Composition for immunizing against staphylococcus aureus

0001(Technical field) The present invention relates to antigens derived from S. aureus and their use in immunization.

0002(Background technology) Staphylococcus aureus is a Gram-positive spherical bacterium. The annual US mortality rate exceeds the mortality rate of any other infection, including HIV / AIDS, and S. aureus is a major cause of bloodstream, lower respiratory tract, skin and soft tissue infections. There are currently no approved vaccines. StaphVAX, a vaccine based on a mixture of surface polysaccharides from bacterial types 5 and 8^TMCould not reduce infection when compared to the placebo group in a 2005 phase III clinical trial.

0003Non-Patent Document 1 reports that the "V710" vaccine from Merck and Intercell is undergoing a phase 2/3 trial in patients undergoing cardiothoracic surgery. The V710 vaccine is based on the single antigen IsdB, which is a conserved iron-sequestering cell-surface protein [Non-Patent Document 2].

0004S. aureus causes a range of diseases ranging from mild skin infections to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, bloodstream, endocarditis, toxic shock syndrome, organ abscesses and sepsis. Is. Bacteria have multiple virulence factors that are expressed differently at different stages of their life cycle, so vaccines that can prevent one disease may not be able to prevent another. For example, the V710 vaccine may be effective against blood diffusion of S. aureus, but may not be effective against pneumonia and may not elicit any opsonic activity. One object of the present invention is to provide a vaccine that can protect against blood diffusion and pneumonia and can also elicit an opsonic response.

<p num="0005"><nplcit num="1"><text>Sheridan,Nature Biotechnology (2009) 27:499-501.</text></nplcit><nplcit num="2"><text>Kuklin et al., Infect Immun. (2006) 74 (4): 2215-23.</text></nplcit></p>

<p num="0006"> Therefore, there is still a need to identify further improved antigens for use in S. aureus vaccines, especially for vaccines useful for multiple S. aureus pathologies.</p>

<p num="0007"> (Disclosure of Invention) We have identified a variety of S. aureus polypeptides that are useful for immunization, either alone or in combination. These polypeptides may be combined with S. aureus sugars or other S. aureus polypeptides. Antigens are useful in S. aureus vaccines, but can also be used as components in vaccines for immunization against multiple pathogens.</p><p num="0008"> We have the following 36 polypeptides: clfA, clfB, coA, eap, ebhA, ebpS, efb, emp, esaC, esxA, esxB, FnBA, FnBB, Hla, hlgB, hlgC, isdA, isdB, isdC, We identified isdG, isdH, isdI, lukD, lukE, lukF, lukS, nuc, sasA, sasB, sasC, sasD, sasF, sdrC, sdrD, spa, and sdrE2. This set of antigens is referred to herein as the "first antigen group". Therefore, the present invention is an immunogenic composition containing a combination of antigens, wherein the combination is (1) clfA antigen; (2) clfB antigen; (3) coA antigen; (4) eap antigen; (5). ) EbhA antigen; (6) ebpS antigen; (7) efb antigen; (8) emp antigen; (9) esaC antigen; (10) esxA antigen; (11) esxB antigen; (12) FnBA antigen; (13) FnBB Antigens; (14) Hla antigens; (15) hlgB antigens; (16) hlgC antigens; (17) isdA antigens; (18) isdB antigens; (19) isdC antigens; (20) isdG antigens; (21) isdH antigens; (22) isdI antigen; (23) lukD antigen; (24) lukE antigen; (25) lukF antigen; (26) lukS antigen; (27) nuc antigen; (28) sasA antigen; (29) sasB antigen; (30) ) SasC antigen; (31) sasD antigen; (32) sasF antigen; (33) sdrC antigen; (34) sdrD antigen; (35) spa antigen; A composition containing 2, 3, 4, 5, 6 or more) antigens is provided.</p><p num="0009"> Of the first antigen group, the antigen is preferably a subset of 16 of the 36 polypeptides: clfA, clfB, emp, esaC, esxA, esxB, hla, isdA, isdB, isdC, sasD, sasF, sdrC, Selected from sdrD, spa and sdrE2. Therefore, the present invention is an immunogenic composition containing a combination of antigens, wherein the combination is selected from the group consisting of 16 or more antigens (that is, 2, 3, 4, 5, 6 or more). ) Is provided.</p><p num="0010"> We have described the following 128 polypeptides:</p><p num="0011"><chemistry num="1"><img id="000002" he="66" wi="153" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>Was also identified. This set of antigens is referred to herein as the "second antigen group". Therefore, the present invention is an immunogenic composition containing a combination of antigens, wherein the combination is (1) sta001 antigen; (2) sta002 antigen; (3) sta003 antigen; (4) sta004 antigen; (5). ) Sta005 antigen; (6) sta006 antigen; (7) sta007 antigen; (8) sta008 antigen; (9) sta009 antigen; (10) sta010 antigen; (11) sta011 antigen; (12) sta012 antigen; (13) sta013 Antigen; (14) sta014 antigen; (15) sta015 antigen; (16) sta016 antigen; (17) sta017 antigen; (18) sta018 antigen; (19) sta019 antigen; (20) sta020 antigen; (21) sta021 antigen; (22) sta022 antigen; (23) sta023 antigen; (24) sta024 antigen; (25) sta025 antigen; (26) sta026 antigen; (27) sta027 antigen; (28) sta028 antigen; (29) sta029 antigen; (30) ) Sta030 antigen; (31) sta031 antigen; (32) sta032 antigen; (33) sta033 antigen; (34) sta034 antigen; (35) sta035 antigen; (36) sta036 antigen; (37) sta037 antigen; (38) sta038 Antigen; (39) sta039 antigen; (40) sta040 antigen; (41) sta041 antigen; (42) sta042 antigen; (43) sta043 antigen; (44) sta044 antigen; (45) sta045 antigen; (46) sta046 antigen; (47) sta047 antigen; (48) sta048 antigen; (49) sta049 antigen; (50) sta050 antigen; (51) sta051 antigen; (52) sta052 antigen; (53) sta053 antigen; (54) sta054 antigen; (55) ) Sta055 antigen; (56) sta056 antigen; (57) sta057 antigen; (58) sta058 antigen; (59) sta059 antigen; (60) sta060 antigen;</p><p num="0012"> Of the second antigen group of 128 antigens, the preferred subset of 113 antigens is the list with (81) and (107)-(120) removed.</p><p num="0013"> Of the second antigen group, 27 subsets of the 128 polypeptides are referred to herein as the "third antigen group", ie.</p><p num="0014"><chemistry num="2"><img id="000003" he="17" wi="155" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>Is. The present invention is an immunogenic composition containing a combination of antigens, wherein the combination contains two or more (ie, 2, 3, 4, 5, 6 or more) antigens selected from the third antigen group. Provide things.</p><p num="0015"> 101 antigens in the second antigen group but not in the third antigen group are referred to herein as the "fourth antigen group". Of the fourth antigen group of 101 antigens, a preferred subset of 86 antigens is the list above with (81) and (107)-(120) removed. Therefore, the second antigen group consists of a combination of the third antigen group and the fourth antigen group.</p><p num="0016"> Of the second antigen group, eight subsets of the 128 polypeptides are referred to herein as the "fifth antigen group", namely sta004, sta006, sta007, sta011, sta028, sta060, sta098 and sta112. .. The present invention is an immunogenic composition containing a combination of antigens, wherein the combination contains two or more (ie, 2, 3, 4, 5, 6 or more) antigens selected from the fifth antigen group. Provide things.</p><p num="0017"> Of the 36 antigens in the first antigen group, there are 630 possible pairs of different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 630 pairs.</p><p num="0018"> Of the 128 antigens in the second antigen group, there are 8128 pairs of possible different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 8128 pairs.</p><p num="0019"> Of the 113 preferred antigens in the second antigen group, there are 6328 possible pairs of different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 6328 pairs.</p><p num="0020"> Of the 27 preferred antigens in the third antigen group, there are 351 possible pairs of different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 351 pairs.</p><p num="0021"> Of the 101 antigens in the 4th antigen group, there are 5050 possible pairs of different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 5050 pairs.</p><p num="0022"> Of the 86 preferred antigens in the 4th antigen group, there are 3655 possible pairs of different antigens. All such pairs are disclosed herein and are part of the present invention. Accordingly, the present invention provides an immunogenic composition comprising a pair of antigens, wherein the pair is one of the 3655 pairs.</p><p num="0023"> In certain embodiments, the composition comprises at least one antigen selected from the first antigen group (ie, 1, 2, 3, 4, 5, 6 or more) and at least one antigen selected from the second antigen group. Includes (ie 1, 2, 3, 4, 5, 6 and above). The antigen from the first antigen group may be selected from a preferred subset of 16 antigens, and the antigen from the second antigen group may be selected from the third or fifth antigen group.</p><p num="0024"> The present invention is an immunogenic composition comprising a combination of antigens, wherein the combination is (1) clfA antigen; (2) clfB antigen; (3) sdrE2 antigen; (4) sdrC antigen; (5) SasF. Antigens; (6) emp antigens; (7) sdrD antigens; (8) spa antigens; (9) esaC antigens; (10) esxA antigens; (11) esxB antigens; (12) sta006 antigens; (13) isdC antigens; (14) hla antigen; (15) sta011 antigen; (16) isdA antigen; (17) isdB antigen; (18) sasF antigen 2 or more selected from the group (that is, 2, 3, 4, 5, 6 or more) ) Antigens are also provided. This group of 18 antigens is sometimes referred to herein as the "sixth antigen group".</p><p num="0025"> The present invention is an immunogenic composition comprising a combination of antigens, wherein the combination is (1) esxA antigen, (2) esxB antigen, (3) sta006 antigen, (4) hla antigen and / or (5). Also provided are compositions containing two or more (ie, 2, 3, 4 or 5) antigens selected from the group consisting of sta011 antigens. The composition may also include an adjuvant, such as an aluminum hydroxide adjuvant.</p><p num="0026"> An advantageous combination of the present invention is one in which two or more antigens act synergistically. Thus, the protection against S. aureus disease achieved by their combination administration goes beyond what is predicted by the mere addition of their individual protective potency.</p><p num="0027"> Specific combinations of problems include, but are not limited to,: (1) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen and an isdC antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. (2) An immunogenic composition containing sasD antigen, clfB antigen and sdrC antigen. (3) An immunogenic composition containing sasD antigen, clfB antigen, sdrC antigen and clfA antigen. (4) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen, an isdC antigen and a sta011 antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. (5) An immunogenic composition containing sasD antigen, clfB antigen, sdrC antigen and sta006 antigen.(6) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen, an isdC antigen and an hla antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. (7) An immunogenic composition containing sasD antigen, clfB antigen, sdrC antigen and esxA antigen. (8) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen and an hla antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation.(9) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen, an isdC antigen and an esxA antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. (10) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen and a sta011 antigen. The esxA and esxB antigens may be combined as a hybrid polypeptide, eg, EsxAB hybrid, as discussed below. (11) An immunogenic composition containing an esxA antigen, an esxB antigen and a sta011 antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. (12) An immunogenic composition containing sasD antigen, clfB antigen, sdrC antigen and spa antigen.(13) An immunogenic composition containing an esxA antigen, an esxB antigen, an isdA antigen, a sta006 antigen, a sta011 antigen and a spa antigen. The esxA and esxB antigens may be combined as a hybrid polypeptide, eg, EsxAB hybrid, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. The spa antigen may be a fragment of a full-length spa antigen, such as a Spa (D) domain mutated to disrupt or reduce binding to IgG Fc. (14) An immunogenic composition containing esxA antigen, esxB antigen, Hla antigen, sta006 antigen and sta011 antigen. The esxA and esxB antigens may be combined as a hybrid polypeptide, eg, EsxAB hybrid, as discussed below. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation.(15) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen, an isdC antigen and an sdrE2 antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. (16) An immunogenic composition containing an esxA antigen, an esxB antigen and an hla antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. (17) An immunogenic composition containing hla antigen, isdA antigen, sta006 antigen and sta011 antigen. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation.(18) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen and an isdA antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. (19) An immunogenic composition containing sasD antigen, clfB antigen, sdrC antigen and hla antigen. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. (20) An immunogenic composition comprising Hla antigen, sta006 antigen and sta011 antigen. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation.(21) An immunogenic composition containing an esxA antigen and an esxB antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. (22) An immunogenic composition containing an esxA antigen, an esxB antigen and a sta006 antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. (23) An immunogenic composition comprising spa antigen, sta006 antigen and sta011 antigen. The spa antigen may be a fragment of the full-length spa antigen, such as the Spa (D) domain mutated to disrupt or reduce binding to IgG Fc.(24) An immunogenic composition containing an esxA antigen, an esxB antigen, an isdA antigen, a sta006 antigen and a sta011 antigen. The esxA and esxB antigens may be combined as a hybrid polypeptide, eg, EsxAB hybrid, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. (25) An immunogenic composition comprising the sta006 antigen and the sta011 antigen. (26) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen, an isdA antigen and a clfB antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. The clfB antigen may be a fragment of the full-length clfB antigen, eg, SEQ ID NO: 163. (27) An immunogenic composition comprising the sta006 antigen, the sta011 antigen and the sta019 antigen.(28) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen, an hla antigen and a clfB antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The clfB antigen may be a fragment of the full-length clfB antigen, eg, SEQ ID NO: 163. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. (29) An immunogenic composition comprising a sta006 antigen, a sta011 antigen, a sta019 antigen and an hla antigen. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. (30) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen, a sta011 antigen and a clfB antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The clfB antigen may be a fragment of the full-length clfB antigen, eg, SEQ ID NO: 163.(31) An immunogenic composition comprising spa antigen, esxA antigen, esxB antigen, sta006 antigen and sta011 antigen. The spa antigen may be a fragment of a full-length spa antigen, such as a Spa (D) domain mutated to disrupt or reduce binding to IgG Fc. The esxA and esxB antigens may be combined as a hybrid polypeptide, eg, EsxAB hybrid, as discussed below. (32) An immunogenic composition containing an sdrD antigen, an sdrE2 antigen, an isdC antigen and an esxB antigen. The sdrD and sdrE2 antigens can be usefully combined as a hybrid polypeptide, eg, an SdrDE hybrid with the sdrE2 antigen downstream of the sdrD antigen, as discussed below. (33) An immunogenic composition comprising esxA antigen, esxB antigen, sta006 antigen, sta011 antigen and sta019 antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below.(34) An immunogenic composition containing an esxA antigen, an esxB antigen, a sta006 antigen, an isdA antigen and an sdrD antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157. The sdrD antigen may be a fragment of the full-length sdrD antigen, eg, SEQ ID NO: 156. (35) An immunogenic composition comprising an esxA antigen, an esxB antigen and an isdA antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. The isdA antigen may be a full-length isdA antigen fragment, eg, SEQ ID NO: 157.(36) An immunogenic composition comprising sasD antigen, clfB antigen, sdrC antigen, esxA antigen and esxB antigen. The esxA and esxB antigens can be usefully combined as a hybrid polypeptide, eg, an EsxAB hybrid having an esxB antigen downstream of the esxA antigen, as discussed below. (37) An immunogenic composition comprising Hla antigen, spa antigen, sta006 antigen and sta011 antigen. The Hla antigen may be, for example, a detoxifying variant containing the H35L mutation. The spa antigen may be a fragment of a full-length spa antigen, such as a Spa (D) domain mutated to disrupt or reduce binding to IgG Fc.</p><p num="0028"> In some embodiments, any of these 37 compositions may comprise additional staphylococcal antigens, the additional antigens of which may be polypeptides and / or sugars. For example, they can usually also include, for example, one or more S. aureus capsular sugar conjugates (s) for serotype 5 and / or serotype 8 strains. Including one or both of such conjugates is particularly useful for combinations (8), (10), (20), (23), (25), (31) and (37).</p><p num="0029"> In other embodiments, these 37 compositions are free of additional staphylococcal polypeptide antigens. In other embodiments, these 37 compositions are free of additional staphylococcal antigens. In other embodiments, these 37 compositions are free of additional antigens.</p><p num="0030"> The present invention is: (a) 80% or more identity with SEQ ID NO: 151 (eg 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98). %, 99%, 99.5% or more) and / or (b) at least "n" contiguous amino acids from amino acids 1-97 of SEQ ID NO: 151 and at least "n" from amino acids 104-207 of SEQ ID NO: 151 Fragments with continuous amino acids (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90) , 100, 150, 200, 250 or more)) are also provided. The present invention has (a) 80% or more identity with SEQ ID NO: 152 (eg, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98). %, 99%, 99.5% or more) and / or (b) at least "n" contiguous amino acids from amino acids 1-104 of SEQ ID NO: 152 and at least "n" from amino acids 111-207 of SEQ ID NO: 152 Fragments with continuous amino acids (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90) , 100, 150, 200, 250 or more)) are also provided. These polypeptides can elicit antibodies (eg, when administered to humans) that recognize both the wild-type staphylococcal protein containing SEQ ID NO: 10 and the wild-type staphylococcal protein containing SEQ ID NO: 11. Thus, the immune response recognizes both antigens esxA and esxB. The preferred fragment of (b) provides an epitope from SEQ ID NO: 10 and an epitope from SEQ ID NO: 11. The present invention also provides an immunogenic composition comprising a combination of such a protein with an adjuvant such as an aluminum hydroxide adjuvant.</p><p num="0031"> The present invention has (a) 80% or more identity with SEQ ID NO: 241 (eg 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98). %, 99%, 99.5% or more) and / or (b) at least "n" contiguous amino acid fragments from amino acids 1-96 of SEQ ID NO: 241 and at least from amino acids 103-205 of SEQ ID NO: 241 Fragments of "n" continuous amino acids (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, Polypeptides comprising an amino acid sequence are also provided, including (90, 100, 150, 200, 250 and above). These polypeptides (eg, SEQ ID NO: 250) provide antibodies (eg, when administered to humans) that recognize both the wild-type staphylococcal protein containing SEQ ID NO: 10 and the wild-type staphylococcal protein containing SEQ ID NO: 11. Can be evoked. Thus, the immune response recognizes both antigens esxA and esxB. The preferred fragment of (b) provides an epitope from SEQ ID NO: 10 and an epitope from SEQ ID NO: 11. The present invention also provides an immunogenic composition comprising a combination of such a protein with an adjuvant such as an aluminum hydroxide adjuvant.</p><p num="0032"> The present invention is a polypeptide comprising a staphylococcal hemolysin sequence, wherein the sequence does not contain a sequence having at least 90% identity with SEQ ID NO: 217, but elicits an antibody capable of killing staphylococci. Polypeptides that can be provided are also provided. Polypeptides are 80% or more identical to SEQ ID NO: 218 (eg 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99). 1st sequence with%, 99.5% or more) and 80% or more identity with SEQ ID NO: 219 (eg 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96) It may have a second sequence having%, 97%, 98%, 99%, 99.5% or more), where the first and second sequences are directly bonded or less than 40 amino acids (%, 97%, 98%, 99%, 99.5% or more). For example, they are joined by an intervening amino acid sequence having 35 amino acids, 30 amino acids, 25 amino acids, 20 amino acids, 15 amino acids, 10 amino acids, 5 amino acids). SEQ ID NOs: 189 and 216 are examples of such polypeptides in which the first and second sequences are joined by the tetrapeptide PSGS sequence (SEQ ID NO: 225).</p><p num="0033"> The present invention relates to Sta011 antigen and Ca.⁺⁺An immunogenic composition comprising an ion is also provided. Antigen and Ca⁺⁺The ions may form a complex, for example, the atoms in the antigen are Ca.⁺⁺It may be coordinated to an ion. The immunogenic composition may also include an adjuvant.</p><p num="0034"> The present invention also provides an oligomer of the Sta011 antigen and an immunogenic composition comprising such an oligomer. Oligomers can be dimers, trimmers, tetramers, pentamers, hexamers, heptamers, octamers or longer. Oligomer is Ca⁺⁺The composition, which may contain ions and contains the Sta011 oligomer, is a Ca of 5 to 500 mM.⁺⁺It may contain ions.</p><p num="0035"> (Additional polypeptide antigen) In addition to antigens from the various antigenic groups of the invention, the immunogenic composition comprises one or more of the following S. aureus antigens (or antigens comprising (s) immunogenic fragments thereof): It may enhance the efficacy of the immune response evoked by the composition against S. aureus [see, eg, References 3-10]:.AhpC .AhpF Autolytic amidase Autolytic glucosaminidase Collagen binding protein CAN .EbhB .GehD lipase Heparin-binding protein HBP (17 kDa) Laminin receptor .MAP .MntC (also known as SitC) .MRPII .Npase .ORF0594 .ORF0657n .ORF0826 .PBP4 .RAP (RNA III activated protein) .Sai-1 .SasK .SBI .SdrG .SdrH .SSP-1 .SSP-2 Vitronectin binding protein (Combination with sugar) The individual antigens identified in the antigen group of the present invention may be used in combination with the conjugated sugar antigen. Therefore, the present invention (1) With one or more antigens selected from the 1st, 2nd, 3rd or 4th antigen group (as defined above), (2) With one or more conjugates of S. aureus exopolysaccharide and carrier protein Provided is an immunogenic composition comprising the combination of.</p><p num="0036"> The conjugate used in component (2) of this combination includes a sugar moiety and a carrier moiety. The sugar moiety is from the extracellular polysaccharide of S. aureus, which is poly-N-acetylglucosamine (PNAG). The sugar may be a polysaccharide having a size that occurs during the purification of exopolysaccharide from a bacterium, or it may be an oligosaccharide achieved by fragmentation of such a polysaccharide, eg, the size It can vary from over 400 kDa to between 75 and 400 kDa, or between 10 and 75 kDa, or in repeating units up to 30. The sugar moiety can have varying degrees of N-acetylation, and as described in Reference 11, PNAG may be N-acetylated to less than 40% (eg, 35, 30, 20, Less than 15, 10 or 5% are N-acetylated; deacetylated PNAGs are also known as dPNAGs). Deacetylated epitopes of PNAG can elicit antibodies that can mediate opsonin killing. PNAG may or may not be O-succinylated, eg, it may be O-succinylated with less than 25, 20, 15, 10, 5, 2, 1 or less than 0.1% residues. ..</p><p num="0037"> The present invention (1) One or more antigens selected from the first, second, third or fourth antigen group, and (2) With one or more conjugates of S. aureus capsular sugar and carrier protein An immunogenic composition comprising a combination of</p><p num="0038"> The conjugate used in component (2) of this combination includes a sugar moiety and a carrier moiety. The sugar moiety is from S. aureus capsular sugar. The sugar may be a polysaccharide having a size that occurs during purification of the capsular polysaccharide from a bacterium, or it may be an oligosaccharide achieved by fragmentation of such a polysaccharide. Capsular sugar is any suitable strain of S. aureus (or any bacterium with similar or identical sugars), such as type 5 and / or type 8 S. aureus strains and / or type 336 S. aureus strains. You can get it from. Most strains of infectious S. aureus contain either type 5 or type 8 capsular sugar. Both have FucNAcp in their repeating units and ManNAcA that can be used to introduce sulfhydryl groups for ligation. The repeating unit of type 5 sugar is 4) -β-D-ManNAcA- (1 4) -α-L-FucNAc (3OAc)-(1 3) -β-D-FucNAc- (1 ). , The repeating unit of type 8 sugar is 3) -β-D-ManNAcA (4OAc)-(1 3) -α-L-FucNAc (1 3) -α-D-FucNAc (1 . Type 336 sugar is a β-linked hexosamine that does not have O-acetylation [12, 13] and is cross-reactive with antibodies produced against strain 336 (ATCC 55804). Type 5 and 8 sugars The combination of is typical, and type 336 sugar may be added to this pair [14].</p><p num="0039"> The present invention (1) One or more antigens selected from the first, second, third or fourth antigen group, and (2) One or more conjugates of S. aureus exopolysaccharide and carrier protein, and (3) One or more conjugates of S. aureus capsule sugar and carrier protein An immunogenic composition comprising a combination of</p><p num="0040"> The carrier portion of these conjugates is usually a protein, but usually not that of the antigen of (1). Typical carrier proteins are diphtheria or tetanus toxins, or bacterial toxins such as toxoids or variants or fragments thereof. CRM197 diphtheria toxin mutant [15] is useful. Other suitable carrier proteins include N. meningitidis outer membrane protein complex [16], synthetic peptides [17, 18], heat shock proteins [19, 20], pertussis proteins [21, 22], cytokines [23], Multiple human CD4s from phosphorus cytokines [23], hormones [23], growth factors [23], antigens derived from various pathogens⁺Artificial proteins containing T cell epitopes [24], such as N19 [25], proteins D [26-28] from H. influenzae, neumoricin [29] or non-toxic derivatives thereof [30], Streptococcus pneumoniae surface protein PspA Includes [31], iron uptake protein [32], toxin A or B [33] from C. difficile, recombinant P. aeruginosa exoprotein A (rEPA) [34], and the like. In some embodiments, the carrier protein is an S. aureus protein, such as an antigen selected from the first, second, third or fourth antigen group.</p><p num="0041"> If the composition comprises more than one conjugate, each conjugate may use the same carrier protein or different carrier proteins.</p><p num="0042"> The conjugate may have excess carriers (w / w) or excess sugar (w / w). In some embodiments, the conjugates may contain substantially equal weights of each.</p><p num="0043"> The carrier molecule may be covalently attached to the carrier, either directly or via a linker. Direct ligation to the protein may be achieved, for example, by reductive amination between the sugar and the carrier, as described, for example, in References 35 and 36. The sugar may first need to be activated, for example by oxidation. Linking via a linker group may be made using any known procedure, such as those described in references 37 and 38. The preferred type of linkage is the free -NH₂It can be formed by coupling a group (eg, introduced into a glucan by amination) with adipic acid (eg, using diimide activation), and then coupling the protein to the resulting sugar-adipic acid intermediate. [39, 40], adipic acid linker. Another preferred type of linkage is a carbonyl linker that can be formed by forming a carbamate linkage by reaction of the free hydroxyl group of the sugar CDI [41, 42] with the subsequent reaction with the protein. Other linkers include β-propionamide [43], nitrophenyl-ethylamine [44], haloacyl halides [45], glycoside linkages [46], 6-aminocaproic acid [47], ADH [48], C.₄~C₁₂Including part [49] and so on. Carbodiimide condensation can also be used [50].</p><p num="0044"> The PNAG conjugate can be a carrier protein in a variety of manners, eg, a) adding a linker containing a maleimide group to activate the PNAG to form an activated PNAG, and b) adding a linker containing a sulfhydryl group. A process comprising the steps of forming an activated carrier protein by activating the PNAG and c) reacting the activated PNAG with the activated carrier protein to form a PNAG-carrier protein conjugate, or a) The step of forming an activated PNAG by adding a linker containing a sulfhydryl group and activating the PNAG, and b) forming an activated carrier protein by adding a linker containing a maleimide group and activating the carrier protein. A process involving c) reacting the activated PNAG with the activated carrier protein to form a PNAG-carrier protein conjugate, or a) adding a linker containing a sulfhydryl group to activate the PNAG. The step of forming an activated PNAG by activating, b) the step of forming an activated carrier protein by activating a carrier protein by adding a linker containing a sulfhydryl group, and c) activating with an activated PNAG. It can be prepared by a process comprising reacting with a carrier protein to form a PNAG-carrier protein conjugate.</p><p num="0045"> The individual antigens identified in the antigen group of the present invention can be used as carrier proteins for exopolysaccharides to form covalent conjugates. Therefore, the present invention is an immunogenic composition comprising a conjugate of (1) an antigen selected from the first, second, third and fourth antigen groups and (2) S. aureus exopolysaccharide. I will provide a. The present invention also provides an immunogenic composition comprising a conjugate of (1) an antigen selected from the first, second, third and fourth antigen groups and (2) S. aureus capsule sugar. .. Further features of such conjugates are described above. These conjugates may be combined with any of the antigens disclosed herein.</p><p num="0046"> (Combination with non-staphylococcal antigen) The individual antigens identified in the antigen group of the present invention may be used in combination with non-staphylococcal antigens, especially antigens from bacteria associated with nosocomial infections. Therefore, the present invention (1) With one or more antigens selected from the 1st, 2nd, 3rd and 4th antigen groups (as defined above). (2) With one or more antigens selected from the group consisting of Clostridium difficile, Pseudomonas aeruginosa, Candida albicans and enteropathogenic Escherichia coli Provided is an immunogenic composition comprising the combination of.</p><p num="0047"> Further suitable antigens for use in combination with the staphylococcal antigens of the present invention are listed on pages 33-46 of reference 51.</p><p num="0048"> (1st antigen group) (clfA) The "clfA" antigen is annotated as "clamping factor A". In the NCTC8325 strain, clfA is SAOUHSC_00812 and has the amino acid sequence of SEQ ID NO: 1 (GI: 88194572). In the Newman strain, this is nwmn_0756 (GI: 151220968).</p><p num="0049"> Useful clfA antigens can elicit antibodies that recognize SEQ ID NO: 1 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 1 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 1 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These clfA proteins contain variants of SEQ ID NO: 1. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 1. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 1 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 1. It holds one epitope. The last 368 C-terminal amino acids of SEQ ID NO: 1 can be conveniently removed. The first 39 N-terminal amino acids of SEQ ID NO: 1 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0050"> SEQ ID NO: 224 is a useful fragment of SEQ ID NO: 1 ("ClfA"._40-559"). This fragment has the long repeating region near the C-terminus of SEQ ID NO: 1 removed.</p><p num="0051"> (clfB) The "clfB" antigen is annotated as "clamping factor B". In the NCTC8325 strain, clfB is SAOUHSC_02963 and has the amino acid sequence of SEQ ID NO: 2 (GI: 88196585). In the Newman strain, this is nwmn_2529 (GI: 151222741).</p><p num="0052"> A useful clfB antigen can elicit an antibody that recognizes SEQ ID NO: 2 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 2 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 2 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These clfB proteins contain variants of SEQ ID NO: 2. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 2. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 2, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 2. It holds one epitope. The last 40 C-terminal amino acids of SEQ ID NO: 2 can be conveniently removed. The first 44 N-terminal amino acids of SEQ ID NO: 2 can be conveniently removed. Other fragments have one or more protein domains removed. Since ClfB is a long protein in nature, the use of fragments aids in, for example, purification, handling, fusion and expression.</p><p num="0053"> SEQ ID NO: 163 is a useful fragment of SEQ ID NO: 2 ("ClfB"._45-552"). This fragment contains the most exposed domain of ClfB and is more easily used on an industrial scale. It also reduces antigen similarity to human proteins. Another useful fragment of ClfB based on the 3-domain model is ClfB._45-360(Also known as CLfB-N12; SEQ ID NO: 196), ClfB_212-542(Also known as CLfB-N23; SEQ ID NO: 197) and ClfB_360-542(Also known as CLfB-N3; SEQ ID NO: 198).</p><p num="0054"> (with the) The "coA" antigen is annotated as "coagulase Coa". In the NCTC8325 strain, coA is SAOUHSC_00192 and has the amino acid sequence of SEQ ID NO: 3 (GI: 88194002). In the Newman strain, this is nwmn_0166 (GI: 151220378).</p><p num="0055"> Useful coA antigens can elicit antibodies that recognize SEQ ID NO: 3 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 3 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 3 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These coA proteins include variants of SEQ ID NO: 3. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 3. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 3, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 3. It holds one epitope. The first 14 N-terminal amino acids of SEQ ID NO: 3 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0056"> (eap) The "eap" antigen has been annotated as a "MHC class II analog protein". In the NCTC8325 strain, eap is SAOUHSC_02161 and has the amino acid sequence of SEQ ID NO: 4 (GI: 88195840). In the Newman strain, this is nwmn_1872 (GI: 151222084).</p><p num="0057"> Useful eap antigens can elicit antibodies that recognize SEQ ID NO: 4 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 4 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 4 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These eap proteins contain variants of SEQ ID NO: 4. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 4. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 4, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 4. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 4 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0058"> (ehA) The "ebhA" antigen is annotated as "EbhA". In the NCTC8325 strain, ebhA is SAOUHSC_01447 and has the amino acid sequence of SEQ ID NO: 5 (GI: 88195168).</p><p num="0059"> Useful ebhA antigens can elicit antibodies that recognize SEQ ID NO: 5 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 5 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 5 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These ebhA proteins include variants of SEQ ID NO: 5. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 5. Other preferred fragments are one or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or multiple amino acids from the C-terminus of SEQ ID NO: 5. One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 5. It holds one epitope. The first 39 N-terminal amino acids of SEQ ID NO: 5 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0060"> (ebpS) The "ebpS" antigen has been annotated as the "elastin-binding protein EbpS". In the NCTC8325 strain, ebpS is SAOUHSC_01501 and has the amino acid sequence of SEQ ID NO: 6 (GI: 88195217). In the Newman strain, this is nwmn_1389 (GI: 151221601).</p><p num="0061"> A useful ebpS antigen can elicit an antibody that recognizes SEQ ID NO: 6 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 6 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 6 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These ebpS proteins contain variants of SEQ ID NO: 6. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 6. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 6 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 6. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0062"> SEQ ID NO: 165 is a useful fragment of SEQ ID NO: 6 (EbpS._1-198"). This fragment contains the most exposed domain of EbpS and is more easily used on an industrial scale. It also reduces antigen similarity to human proteins.</p><p num="0063"> (efb) The "efb" antigen has been annotated as a "fibrinogen-binding protein cleaved form". In the NCTC8325 strain, efb is SAOUHSC_01114 and has the amino acid sequence of SEQ ID NO: 7 (GI: 88194860). In the Newman strain, this is nwmn_1069 (GI: 151221281).</p><p num="0064"> Useful efb antigens can elicit antibodies that recognize SEQ ID NO: 7 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 7 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 7 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These efb proteins include variants of SEQ ID NO: 7. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 7. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 7, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 7. It holds one epitope. The first 14 N-terminal amino acids of SEQ ID NO: 7 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0065"> (emp) The "emp" antigen is annotated as an "extracellular matrix and plasma binding protein". In the NCTC8325 strain, emp is SAOUHSC_00816 and has the amino acid sequence of SEQ ID NO: 8 (GI: 88194575). In the Newman strain, this is nwmn_0758 (GI: 151220970).</p><p num="0066"> Useful emp antigens can elicit antibodies that recognize SEQ ID NO: 8 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 8 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 8 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These emp proteins contain variants of SEQ ID NO: 8. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 8. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 8 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 8. It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 8 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0067"> SEQ ID NOs: 190, 191, 192 and 193 are useful fragments of SEQ ID NO: 8 ("Emp" respectively._35-340","Emp_27-334","Emp_35-334And "Emp_27-147」)。 </p><p num="0068"> (esaC) The "esaC" antigen is annotated as "esaC". In the NCTC8325 strain, esaC is SAOUHSC_00264 and has the amino acid sequence of SEQ ID NO: 9 (GI: 88194069).</p><p num="0069"> Useful esaC antigens can elicit antibodies that recognize SEQ ID NO: 9 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 9 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 9 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These esaC proteins contain variants of SEQ ID NO: 9. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 9. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 9, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 9. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0070"> (esxA) The "esxA" antigen is annotated as a "protein". In the NCTC8325 strain, esxA is SAOUHSC_00257 and has the amino acid sequence of SEQ ID NO: 10 (GI: 88194063).</p><p num="0071"> Useful esxA antigens can elicit antibodies that recognize SEQ ID NO: 10 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 10 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 10 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90 or more)). These esxA proteins contain variants of SEQ ID NO: 10. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 10. Other preferred fragments are one or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or multiple amino acids from the C-terminus of SEQ ID NO: 10. One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 10. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0072"> (esxB) The "esxB" antigen is annotated as "esxB". In the NCTC8325 strain, esxB is SAOUHSC_00265 and has the amino acid sequence of SEQ ID NO: 11 (GI: 88194070).</p><p num="0073"> Useful esxB antigens can elicit antibodies that recognize SEQ ID NO: 11 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 11 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 11 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These esxB proteins include variants of SEQ ID NO: 11. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 11. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 11 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 11. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0074"> (FnBA) The "FnBA" antigen is annotated as "fibronectin binding protein A precursor FnBPA". In the NCTC8325 strain, FnBA is SAOUHSC_02803 and has the amino acid sequence of SEQ ID NO: 12 (GI: 88196438). In the Newman strain, this is nwmn_2399 (GI: 151222611). Proteomics analysis reveals that this protein is secreted or exposed to the surface.</p><p num="0075"> Useful FnBA antigens can elicit antibodies that recognize SEQ ID NO: 12 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 12 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 12 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These FnBA proteins include variants of SEQ ID NO: 12. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 12. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 12, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 12. It holds one epitope. The last 37 C-terminal amino acids of SEQ ID NO: 12 can be conveniently removed. Other fragments have one or more protein domains removed. Since FnBA is a long protein in nature, the use of fragments aids in, for example, purification, handling, fusion and expression.</p><p num="0076"> SEQ ID NO: 166 ("FnBA"_1-511) And 167 (FnBA_512-953") Is a useful fragment of SEQ ID NO: 12. These fragments are more easily used on an industrial scale.</p><p num="0077"> (FnBB) The "FnBB" antigen is annotated as "fibronectin binding protein B FnBPB". In the NCTC8325 strain, FnBB is SAOUHSC_02802 and has the amino acid sequence of SEQ ID NO: 13 (GI: 88196437). In the Newman strain, this is nwmn_2397 (GI: 151222609).</p><p num="0078"> Useful FnBB antigens can elicit antibodies that recognize SEQ ID NO: 13 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 13 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 13 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These FnBB proteins include variants of SEQ ID NO: 13. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 13. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 13 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 13. It holds one epitope. The last 37 C-terminal amino acids of SEQ ID NO: 13 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0079"> (Hla) The "Hla" antigen is an "alpha hemolysin precursor" also known as an "alpha toxin" or simply a "hemolysin". In the NCTC8325 strain, Hla is SAOUHSC_01121 and has the amino acid sequence of SEQ ID NO: 14 (GI: 88194865). In the Newman strain, this is nwmn_1073 (GI: 151221285). Hla is an important toxic determinant produced by most strains of S. aureus and has pore-forming and hemolytic activity. Anti-Hla antibodies can neutralize the harmful effects of toxins in animal models, and Hla is particularly useful for protection against pneumonia.</p><p num="0080"> Useful Hla antigens can elicit antibodies that recognize SEQ ID NO: 14 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 14 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 14 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These Hla proteins contain variants of SEQ ID NO: 14. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 14. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 14, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 14. It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 14 can be conveniently removed (eg, SEQ ID NO: 231 is obtained). C-terminal cleavage can also be used, for example leaving only 50 amino acids (residues 27-76 of SEQ ID NO: 14) [52]. Other fragments have one or more protein domains removed.</p><p num="0081"> Toxicity of Hla can be avoided in the compositions of the invention by chemical inactivation (eg using formaldehyde, glutaraldehyde or other cross-linking agents). However, instead, it is preferred to use a mutant form of Hla from which toxic activity has been removed while preserving its immunogenicity. Such detoxifying variants are already known in the art. One useful Hla antigen is residue 61 of SEQ ID NO: 14 (which is residue 35 of the mature antigen (ie, after removing the first 26 N-terminal amino acids = residue 35 of SEQ ID NO: 231)). Has a mutation in. Thus, residue 61 may not be histidine and may instead be, for example, Ile, Val or preferably Leu. A His-Arg mutation at this position can also be used. For example, SEQ ID NO: 150 is the mature variant Hla-H35L sequence (ie, SEQ ID NO: 231 with the H35L mutation) and a useful Hla antigen comprises SEQ ID NO: 150. Other useful mutations include replacing the long loop with a short sequence, eg, 39 mer at residues 136-174 of SEQ ID NO: 14, SEQ ID NO: 189 (including H35L mutation) and SEQ ID NO: 216 (including H35L mutation). Replace with a tetramer such as PSGS (SEQ ID NO: 225). Another useful mutation replaces residue Y101 with, for example, leucine (SEQ ID NO: 242). Another useful mutation replaces residue D152 with, for example, leucine (SEQ ID NO: 243). Another useful variant replaces residues H35 and Y101 with, for example, leucine (SEQ ID NO: 244). Another useful variant replaces residues H35 and D152 with, for example, leucine (SEQ ID NO: 245).</p><p num="0082"> More useful Hla antigens are disclosed in references 53 and 54.</p><p num="0083"> SEQ ID NOs: 160, 161 and 194 are three useful fragments of SEQ ID NO: 14, respectively (Hla, respectively._27-76","Hla_27-89And "Hla"_27-79"). SEQ ID NOs: 158, 159 and 195 are the corresponding fragments from SEQ ID NO: 150.</p><p num="0084"> One useful Hla sequence is SEQ ID NO: 232, which was used in the examples. It has an N-terminal Met, then an Ala-Ser dipeptide from an expression vector, followed by SEQ ID NO: 150 (from NCTC8325 strain). It is encoded by SEQ ID NO: 233.</p><p num="0085"> (hlgB) The "hlgB" antigen is annotated as "leukocidin f subunit precursor HlgB". In the NCTC8325 strain, hlgB is SAOUHSC_02710 and has the amino acid sequence of SEQ ID NO: 15 (GI: 88196350).</p><p num="0086"> A useful hlgB antigen can elicit an antibody that recognizes SEQ ID NO: 15 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 15 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 15 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These hlgB proteins include variants of SEQ ID NO: 15. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 15. Other preferred fragments are one or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or multiple amino acids from the C-terminus of SEQ ID NO: 15. One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 15. It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 15 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0087"> (hlgC) The "hlgC" antigen has been annotated as "leukocidin s subunit precursor HlgC". In the NCTC8325 strain, hlgC is SAOUHSC_02709 and has the amino acid sequence of SEQ ID NO: 16 (GI: 88196349).</p><p num="0088"> A useful hlgC antigen can elicit an antibody that recognizes SEQ ID NO: 16 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 16 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 16 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These hlgC proteins include variants of SEQ ID NO: 16. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 16. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 16 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 16. It holds one epitope. The first 29 N-terminal amino acids of SEQ ID NO: 16 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0089"> (isdA) The "isdA" antigen is annotated as the "IsdA protein". In the NCTC8325 strain, isdA is SAOUHSC_01081 and has the amino acid sequence of SEQ ID NO: 17 (GI: 88194829). In the Newman strain, this is nwmn_1041 (GI: 151221253).</p><p num="0090"> Useful isdA antigens can elicit antibodies that recognize SEQ ID NO: 17 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 17 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 17 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These isdA proteins include variants of SEQ ID NO: 17. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 17. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 17, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 17 It holds one epitope. The last 38 C-terminal amino acids of SEQ ID NO: 17 can be conveniently removed. The first 46 N-terminal amino acids of SEQ ID NO: 17 can be conveniently removed. Cleavage of SEQ ID NO: 17 excluding the C-terminal 38 mer (starting with the LPKTG motif) is also useful. Other fragments have one or more protein domains removed.</p><p num="0091"> SEQ ID NO: 157 is a useful fragment of SEQ ID NO: 17 (amino acids 40-184 of SEQ ID NO: 17; "IsdA"._40-184), It contains the heme binding site of an intrinsically disordered protein and contains the most exposed domain of the antigen. It also reduces antigen similarity to human proteins. Other useful fragments are disclosed in references 55 and 56.</p><p num="0092"> Since IsdA does not adsorb well to the aluminum hydroxide adjuvant, IsdA present in the composition may not be adsorbed or may be adsorbed to an alternative adjuvant, such as aluminum phosphate.</p><p num="0093"> Anti-IsdA antibodies protect mice against S. aureus abscess formation and lethal challenges [57].</p><p num="0094"> (isdB) The "isdB" antigen is annotated as "nerve filament protein isdB". In the NCTC8325 strain, isdB is SAOUHSC_01079 and has the amino acid sequence of SEQ ID NO: 18 (GI: 88194828). IsdB has been proposed to be used as a vaccine antigen on its own [2], but it may not prevent pneumonia.</p><p num="0095"> Useful isdB antigens can elicit antibodies that recognize SEQ ID NO: 18 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 18 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 18 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These isdB proteins include variants of SEQ ID NO: 18. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 18. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 18, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 18. It holds one epitope. The last 36 C-terminal amino acids of SEQ ID NO: 18 can be conveniently removed. The first 40 N-terminal amino acids of SEQ ID NO: 18 can be conveniently removed. Other fragments have one or more protein domains removed. A useful fragment of IsdB is disclosed in References 56 and 58, for example deleting the internal amino acid of 37 of SEQ ID NO: 18.</p><p num="0096"> Anti-IsdB antibodies protect mice against S. aureus abscess formation and lethal challenges [57].</p><p num="0097"> In some embodiments, the compositions of the invention are free of isdB antigens.</p><p num="0098"> (isdC) The "isdC" antigen is annotated as a "protein". In the NCTC8325 strain, isdC is SAOUHSC_01082 and has the amino acid sequence of SEQ ID NO: 19 (GI: 88194830).</p><p num="0099"> Useful isdC antigens can elicit antibodies that recognize SEQ ID NO: 19 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 19 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 19 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These isdC proteins include variants of SEQ ID NO: 19. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 19. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 19 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 19. It holds one epitope. The last 39 C-terminal amino acids of SEQ ID NO: 19 can be conveniently removed. The first 28 N-terminal amino acids of SEQ ID NO: 19 can be conveniently removed. Other fragments have one or more protein domains removed. A useful fragment of IsdB is disclosed in reference 56.</p><p num="0100"> Reference 59 discloses antigens that conveniently contain epitopes from both IsdB and IsdH.</p><p num="0101"> (isdG) The "isdG" antigen is annotated as "heme-degrading monooxygenase IsdG". In the NCTC8325 strain, isdG is SAOUHSC_01089 and has the amino acid sequence of SEQ ID NO: 20 (GI: 88194836).</p><p num="0102"> Useful isdG antigens can elicit antibodies that recognize SEQ ID NO: 20 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 20 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 20 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These isdG proteins include variants of SEQ ID NO: 20. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 20. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 20, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 20 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0103"> (isdH) The "isdH" antigen is annotated as "isdH". In the NCTC8325 strain, isdH is SAOUHSC_01843 and has the amino acid sequence of SEQ ID NO: 21 (GI: 88195542). In the Newman strain, this is nwmn_1624 (GI: 151221836). This is also known as HarA.</p><p num="0104"> Useful isdH antigens can elicit antibodies that recognize SEQ ID NO: 21 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 21 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 21 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These isdH proteins include variants of SEQ ID NO: 21. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 21. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 21 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 21 It holds one epitope. The last 35 C-terminal amino acids of SEQ ID NO: 21 can be conveniently removed. The first 40 N-terminal amino acids of SEQ ID NO: 21 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0105"> Reference 59 discloses antigens that conveniently contain epitopes from both IsdB and IsdH.</p><p num="0106"> (isdI) The "isdI" antigen is annotated as "heme-degrading monooxygenase IsdI". In the NCTC8325 strain, isdI is SAOUHSC_00130 and has the amino acid sequence of SEQ ID NO: 22 (GI: 88193943).</p><p num="0107"> Useful isdI antigens can elicit antibodies that recognize SEQ ID NO: 22 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 22 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 22 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These isdI proteins include variants of SEQ ID NO: 22. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 22. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 22 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 22 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0108"> (lukD) The "lukD" antigen is annotated as "leucotoxin LukD". In the NCTC8325 strain, lukD is SAOUHSC_01954 and has the amino acid sequence of SEQ ID NO: 23 (GI: 88195647). In the Newman strain, this is nwmn_1718 (GI: 151221930).</p><p num="0109"> A useful lukD antigen can elicit an antibody that recognizes SEQ ID NO: 23 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 23 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 23 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These lukD proteins include variants of SEQ ID NO: 23. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 23. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 23 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 23 It holds one epitope. The last 43 C-terminal amino acids of SEQ ID NO: 23 can be conveniently removed. The first 26 N-terminal amino acids of SEQ ID NO: 23 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0110"> (lukE) The "lukE" antigen is annotated as "leucotoxin LukE". In the NCTC8325 strain, lukE is SAOUHSC_01955 and has the amino acid sequence of SEQ ID NO: 24 (GI: 88195648).</p><p num="0111"> A useful lukE antigen can elicit an antibody that recognizes SEQ ID NO: 24 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 24 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 24 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These lukE proteins include variants of SEQ ID NO: 24. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 24. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 24 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 24 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0112"> (lukF) The "lukF" antigen has been annotated as the "leukocidin / hemolysin toxin family LukF". In the NCTC8325 strain, lukF is SAOUHSC_02241 and has the amino acid sequence of SEQ ID NO: 25 (GI: 88195914).</p><p num="0113"> Useful lukF antigens can elicit antibodies that recognize SEQ ID NO: 25 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 25 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 25 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These lukF proteins include variants of SEQ ID NO: 25. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 25. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 25 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 25 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0114"> (lukS) The "lukS" antigen is annotated as the "estimated leukocidin S subunit LukS". In the NCTC8325 strain, lukS is SAOUHSC_02243 and has the amino acid sequence of SEQ ID NO: 26 (GI: 88195915). In the Newman strain, this is nwmn_1928 (GI: 151222140).</p><p num="0115"> A useful lukS antigen can elicit an antibody that recognizes SEQ ID NO: 26 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 26 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 26 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These lukS proteins contain variants of SEQ ID NO: 26. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 26. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 26 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 26 It holds one epitope. The first 22 N-terminal amino acids of SEQ ID NO: 26 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0116"> (walnut) The "nuc" antigen is annotated as a "thermonuclease precursor". In the NCTC8325 strain, nuc is SAOUHSC_01316 and has the amino acid sequence of SEQ ID NO: 27 (GI: 88195046).</p><p num="0117"> A useful nuc antigen can elicit an antibody that recognizes SEQ ID NO: 27 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 27 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 27 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These nuc proteins contain variants of SEQ ID NO: 27. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 27. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 27 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 27 It holds one epitope. The last 39 C-terminal amino acids of SEQ ID NO: 27 can be conveniently removed. The first 19 N-terminal amino acids of SEQ ID NO: 27 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0118"> (nowA) The "sasA" antigen is annotated as "SasA". In the NCTC8325 strain, sasA is SAOUHSC_02990 and has the amino acid sequence of SEQ ID NO: 28 (GI: 88196609).</p><p num="0119"> Useful sasA antigens can elicit antibodies that recognize SEQ ID NO: 28 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 28 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 28 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sasA proteins contain variants of SEQ ID NO: 28. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 28. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 28 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 28 It holds one epitope. The last 43 C-terminal amino acids of SEQ ID NO: 28 can be conveniently removed. The first 90 N-terminal amino acids of SEQ ID NO: 28 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0120"> (sasB) The "sasB" antigen is annotated as "fmtB protein; SasB". In the NCTC8325 strain, sasB is SAOUHSC_02404 and has the amino acid sequence of SEQ ID NO: 29 (GI: 88196065).</p><p num="0121"> A useful sasB antigen can elicit an antibody that recognizes SEQ ID NO: 29 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 29 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 29 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sasB proteins contain variants of SEQ ID NO: 29. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 29. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 29 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 29 It holds one epitope. The last 39 C-terminal amino acids of SEQ ID NO: 29 can be conveniently removed. The first 38 N-terminal amino acids of SEQ ID NO: 29 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0122"> (sasC) The "sasC" antigen is annotated as "Mrp protein; SasC". In the NCTC8325 strain, sasC is SAOUHSC_01873 and has the amino acid sequence of SEQ ID NO: 30 (GI: 88195570).</p><p num="0123"> A useful sasC antigen can elicit an antibody that recognizes SEQ ID NO: 30 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 30 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 30 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sasC proteins contain variants of SEQ ID NO: 30. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 30. Other preferred fragments are one or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or multiple amino acids from the C-terminus of SEQ ID NO: 30. One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 30 It holds one epitope. The last 36 C-terminal amino acids of SEQ ID NO: 30 can be conveniently removed. The first 37 N-terminal amino acids of SEQ ID NO: 30 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0124"> (sassD) The "sasD" antigen is annotated as a "SasD protein". In the NCTC8325 strain, sasD is SAOUHSC_00094 and has the amino acid sequence of SEQ ID NO: 31 (GI: 88193909).</p><p num="0125"> A useful sasD antigen can elicit an antibody that recognizes SEQ ID NO: 31 (eg when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 31 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 31 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sasD proteins contain variants of SEQ ID NO: 31. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 31. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 31 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 31 It holds one epitope. The first 28 N-terminal amino acids of SEQ ID NO: 31 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0126"> (sasF) The "sasF" antigen is annotated as a "sasF protein". In the NCTC8325 strain, sasF is SAOUHSC_02982 and has the amino acid sequence of SEQ ID NO: 32 (GI: 88196601).</p><p num="0127"> Useful sasF antigens can elicit antibodies that recognize SEQ ID NO: 32 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 32 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 32 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sasF proteins contain variants of SEQ ID NO: 32. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 32. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 32 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 32 It holds one epitope. The last 39 C-terminal amino acids of SEQ ID NO: 32 can be conveniently removed. The first 37 N-terminal amino acids of SEQ ID NO: 32 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0128"> (sdrC) The "sdrC" antigen is annotated as the "sdrC protein". In the NCTC8325 strain, sdrC is SAOUHSC_00544 and has the amino acid sequence of SEQ ID NO: 33 (GI: 88194324).</p><p num="0129"> A useful sdrC antigen can elicit an antibody that recognizes SEQ ID NO: 33 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 33 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 33 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sdrC proteins contain variants of SEQ ID NO: 33. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 33. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 33 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 33 It holds one epitope. The last 38 C-terminal amino acids of SEQ ID NO: 33 can be conveniently removed. The first 50 N-terminal amino acids of SEQ ID NO: 33 can be conveniently removed. Other fragments have one or more protein domains removed. Since SdrC is a long protein in nature, the use of fragments aids in, for example, purification, handling, fusion and expression.</p><p num="0130"> SEQ ID NO: 164 is a useful fragment of SEQ ID NO: 33 ("SdrC"._1-518"). This fragment contains the most exposed domain of SdrC and is more easily used on an industrial scale. It also reduces antigen similarity to human proteins.</p><p num="0131"> (sdrD) The "sdrD" antigen is annotated as the "sdrD protein". In the NCTC8325 strain, sdrD is SAOUHSC_00545 and has the amino acid sequence of SEQ ID NO: 34 (GI: 88194325).</p><p num="0132"> A useful sdrD antigen can elicit an antibody that recognizes SEQ ID NO: 34 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 34 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 34 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sdrD proteins include variants of SEQ ID NO: 34. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 34. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 34 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 34 It holds one epitope. The last 38 C-terminal amino acids of SEQ ID NO: 34 can be conveniently removed. The first 52 N-terminal amino acids of SEQ ID NO: 34 can be conveniently removed. Other fragments have one or more protein domains removed. Since SdrD is a long protein in nature, the use of fragments is very helpful, for example in purification, handling, fusion, expression, etc.</p><p num="0133"> SEQ ID NO: 156 is a useful fragment of SEQ ID NO: 34 ("SdrD"._53-592"). This fragment contains the most exposed domain of SdrD and is more easily used on an industrial scale. It also reduces antigen similarity to human proteins. Another useful fragment with the same C-terminal residue is SdrD_394-592(Also known as SdrD-N3; SEQ ID NO: 199). Another useful fragment is described herein as "SdrD"._CnaBIs SEQ ID NO: 236 (amino acids 593 to 1123 of SEQ ID NO: 34).</p><p num="0134"> (sdrE2) The "sdrE2" antigen is annotated as "Ser-Asp rich fibrinogen / bone sialoprotein binding protein SdrE". In the Newman strain, sdrE2 is NWMN_0525 and has the amino acid sequence of SEQ ID NO: 35 (GI: 151220737).</p><p num="0135"> A useful sdrE2 antigen can elicit an antibody that recognizes SEQ ID NO: 35 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 35 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 35 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sdrE2 proteins contain variants of SEQ ID NO: 35. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 35. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 35 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 35 It holds one epitope. The last 38 C-terminal amino acids of SEQ ID NO: 35 can be conveniently removed. The first 52 N-terminal amino acids of SEQ ID NO: 35 can be conveniently removed. Other fragments have one or more protein domains removed. Since SdrE2 is a long protein in nature, the use of fragments is very helpful, for example in purification, handling, fusion and expression.</p><p num="0136"> SEQ ID NO: 155 is a useful fragment of SEQ ID NO: 35 ("SdrE"._53-632"). This fragment contains the most exposed domain of SdrE2 and is more easily used on an industrial scale. It also reduces antigen similarity to human proteins.</p><p num="0137"> (spa) The "spa" antigen is annotated as "protein A" or "SpA". In the NCTC8325 strain, spa is SAOUHSC_00069 and has the amino acid sequence of SEQ ID NO: 36 (GI: 88193885). In the Newman strain, this is nwmn_0055 (GI: 151220267). All S. aureus strains have five highly homologous immunoglobulin bindings called highly characterized pathogenic factors (the surface protein products tethered to their cell walls are called E, D, A, B and C). It expresses a structural gene for spa (having a domain) [60]. These domains show about 80% identity at the amino acid level, are 56-61 residues long, and are organized as tandem repeats [61]. SpA is synthesized as a precursor protein with an N-terminal signal peptide and a C-terminal sorting signal [62, 63]. Spas tethered to the cell wall are very abundantly presented on the surface of staphylococci [64, 65]. Each of its immunoglobulin binding domains is composed of antiparallel α-helices assembled into a bundle of three helices, the Fc domain of immunoglobulin G (IgG) [66, 67], and the VH triple chain (Fab) of IgM. That is, it can bind to the B cell receptor) [68], the von Bilbrant factor [69] in its A1 domain, and / or the TNF-α receptor I (TNFRI) [70] presented on the surface of the airway epithelium. ..</p><p num="0138"> Useful spa antigens can elicit antibodies that recognize SEQ ID NO: 36 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 36 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 36 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These spa proteins contain variants of SEQ ID NO: 36. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 36. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 36 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 36 It holds one epitope. The last 35 C-terminal amino acids of SEQ ID NO: 36 can be conveniently removed. The first 36 N-terminal amino acids of SEQ ID NO: 36 can be conveniently removed. Other fragments have one or more protein domains removed. Reference 71 suggests that individual IgG-binding domains may be useful immunogens alone or in combination.</p><p num="0139"> SEQ ID NO: 162 is a useful fragment of SEQ ID NO: 36 ("Spa"._37-325"). This fragment contains all five SpA Ig binding domains, which are naturally located in the order E, D, A, B, C from N-terminus to C-terminus, and is the most exposed of SpA. Includes domain. It also reduces antigen similarity to human proteins. Other useful fragments include natural A, B, C, D and to prevent excessive B cell expansion that can occur when spa functions as a B cell superantigen and subsequent apoptosis. / Or you may remove 1, 2, 3 or 4 of the E domain. Other useful fragments, as reported in Reference 71, may contain only 1, 2, 3 or 4 of the natural A, B, C, D and / or E domains, eg SpA (A). ) Domains only and do not contain B ~ E, or SpA (D) domains only and do not contain A, B, C or E, and so on. Thus, spa antigens useful in the present invention may contain 1, 2, 3, 4 or 5 IgG binding domains, ideally having 4 or less.</p><p num="0140"> If the antigen contains only one type of spa domain (eg, only Spa (A) or SpA (D) domain), this is more than one copy of this domain, eg, multiple in a single polypeptide chain. It may include a SpA (D) domain.</p><p num="0141">Individual domains within the antigen can be mutated with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids relative to SEQ ID NO: 36 (eg, residue 3 of domain D). And / or 24, see reference 71, which discloses mutations at residues 46 and / or 53 of domain A). Such variants should not remove the ability of the antigen to elicit the antibody that recognizes SEQ ID NO: 36, but remove the binding of the antigen to IgG and / or other human proteins (eg, human blood proteins). Can be done.</p><p num="0142"> In some embodiments, the spa antigen (a) substitutes one or more amino acids in the IgG Fc-binding subdomains of SpA domains A, B, C, D and / or E that disrupt or reduce binding to IgG Fc. And (b) V_HV of SpA domains A, B, C, D and / or E that disrupts or reduces binding to 3_HIncludes substitutions with one or more amino acid substitutions in a three-binding subdomain. In certain embodiments, the variant SpA comprises at least, or at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more variant SpA domain D peptides.</p><p num="0143"> (Second antigen group) (sta001) The "sta001" antigen is annotated as a "5'-nucleotidase family protein". In the NCTC8325 strain, sta001 is SAOUHSC_00025 and has the amino acid sequence of SEQ ID NO: 37 (GI: 88193846). In the Newman strain, this is nwmn_0022 (GI: 151220234). It is also called Ads A and Sas H and SA0024.</p><p num="0144"> A useful sta001 antigen can elicit an antibody that recognizes SEQ ID NO: 37 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 37 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 37 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta001 proteins include variants of SEQ ID NO: 37. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 37. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 37 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 37 It holds one epitope. The last 34 C-terminal amino acids of SEQ ID NO: 37 can be conveniently removed. The first 38 N-terminal amino acids of SEQ ID NO: 37 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0145"> (sta002) The "sta002" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta002 is SAOUHSC_00356 and has the amino acid sequence of SEQ ID NO: 38 (GI: 88194155). In the Newman strain, this is nwmn_0364 (GI: 151220576).</p><p num="0146"> A useful sta002 antigen can elicit an antibody that recognizes SEQ ID NO: 38 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 38 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 38 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta002 proteins include variants of SEQ ID NO: 38. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 38. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 38 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 38 It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 38 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0147"> SEQ ID NO: 153 ("sta002"_19-187) And 154 (sta002_19-124") Are two useful fragments of SEQ ID NO: 38 that reduce antigen similarity to human proteins.</p><p num="0148"> (sta003) The "sta003" antigen is annotated as a "surface protein". In the NCTC8325 strain, sta003 is SAOUHSC_00400 and has the amino acid sequence of SEQ ID NO: 39 (GI: 88194195). In the Newman strain, this is nwmn_0401 (GI: 151220613).</p><p num="0149"> A useful sta003 antigen can elicit an antibody that recognizes SEQ ID NO: 39 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 39 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 39 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta003 proteins contain variants of SEQ ID NO: 39. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 39. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 39 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 39 It holds one epitope. The first 32 N-terminal amino acids of SEQ ID NO: 39 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0150"> (sta004) The "sta004" antigen is annotated as "siderophore binding protein FatB". In the NCTC8325 strain, sta004 is SAOUHSC_00749 and has the amino acid sequence of SEQ ID NO: 40 (GI: 88194514). In the Newman strain, this is nwmn_0705 (GI: 151220917).</p><p num="0151"> A useful sta004 antigen can elicit an antibody that recognizes SEQ ID NO: 40 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 40 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 40 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta004 proteins contain variants of SEQ ID NO: 40. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 40. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 40 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 40 It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 40 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0152"> (sta005) The "sta005" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta005 is SAOUHSC_01127 and has the amino acid sequence of SEQ ID NO: 41 (GI: 88194870). In the Newman strain, this is nwmn_1077 (GI: 151221289).</p><p num="0153"> A useful sta005 antigen can elicit an antibody that recognizes SEQ ID NO: 41 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 41 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 41 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta005 proteins include variants of SEQ ID NO: 41. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 41. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 41 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 41 It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 41 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0154"> (sta006) The "sta006" antigen is annotated as a "ferrichrome-binding protein" and is also referred to as "FhuD2" in the literature. [72] In the NCTC8325 strain, sta006 is SAOUHSC_02554 and has the amino acid sequence of SEQ ID NO: 42 (GI: 88196199). In the Newman strain, this is nwmn_2185 (GI: 151222397).</p><p num="0155"> A useful sta006 antigen can elicit an antibody that recognizes SEQ ID NO: 42 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 42 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 42 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta006 proteins contain variants of SEQ ID NO: 42. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 42. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 42 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 42 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 42 can be conveniently removed (SEQ ID NO: 246 is obtained). Other fragments have one or more protein domains removed. The morphology of the mutant of sta006 is reported in reference 73. The sta006 antigen may be added lipid using, for example, an acylated N-terminal cysteine. One useful sta006 sequence is SEQ ID NO: 248, which has the Met-Ala-Ser-sequence at the N-terminus.</p><p num="0156"> (sta007) The "sta007" antigen is annotated as a "secretory antigen precursor". In the NCTC8325 strain, sta007 is SAOUHSC_02571 and has the amino acid sequence of SEQ ID NO: 43 (GI: 88196215). In the Newman strain, this is nwmn_2199 (GI: 151222411). Proteomics analysis reveals that this protein is secreted or exposed to the surface.</p><p num="0157"> A useful sta007 antigen can elicit an antibody that recognizes SEQ ID NO: 43 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 43 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 43 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta007 proteins contain variants of SEQ ID NO: 43. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 43. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 43 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 43. It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 43 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0158"> (sta008) The "sta008" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta008 is SAOUHSC_02650 and has the amino acid sequence of SEQ ID NO: 44 (GI: 88196290). In the Newman strain, this is nwmn_2270 (GI: 151222482).</p><p num="0159"> A useful sta008 antigen can elicit an antibody that recognizes SEQ ID NO: 44 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 44 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 44 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta008 proteins include variants of SEQ ID NO: 44. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 44. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 44 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 44 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 44 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0160"> (sta009) The "sta009" antigen is annotated as "immunoglobulin G-binding protein Sbi". In the NCTC8325 strain, sta009 is SAOUHSC_02706 and has the amino acid sequence of SEQ ID NO: 45 (GI: 88196346). In the Newman strain, this is nwmn_2317 (GI: 151222529).</p><p num="0161"> A useful sta009 antigen can elicit an antibody that recognizes SEQ ID NO: 45 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 45 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 45 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta009 proteins contain variants of SEQ ID NO: 45. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 45. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 45 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 45 It holds one epitope. The first 29 N-terminal amino acids of SEQ ID NO: 45 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0162"> (sta010) The "sta010" antigen is annotated as "immune-dominant antigen A". In the NCTC8325 strain, sta010 is SAOUHSC_02887 and has the amino acid sequence of SEQ ID NO: 46 (GI: 88196515). In the Newman strain, this is nwmn_2469 (GI: 151222681). Proteomics analysis reveals that this protein is secreted or exposed to the surface.</p><p num="0163"> A useful sta010 antigen can elicit an antibody that recognizes SEQ ID NO: 46 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 46 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 46 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta010 proteins contain variants of SEQ ID NO: 46. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 46. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 46 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 46 It holds one epitope. The first 29 N-terminal amino acids of SEQ ID NO: 46 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0164"> (sta011) The "sta011" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta011 is SAOUHSC_00052 and has the amino acid sequence of SEQ ID NO: 47 (GI: 88193872).</p><p num="0165"> A useful sta011 antigen can elicit an antibody that recognizes SEQ ID NO: 47 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 47 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 47 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta011 proteins contain variants of SEQ ID NO: 47. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 47. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 47 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 47 It holds one epitope. The first 23 N-terminal amino acids of SEQ ID NO: 47 can be conveniently removed (SEQ ID NO: 247 is obtained). Other fragments have one or more protein domains removed. The sta011 antigen may be lipid-added using, for example, an acylated N-terminal cysteine. One useful sta011 sequence is SEQ ID NO: 249, which has an N-terminal methionine.</p><p num="0166"> The forms of variants of SEQ ID NO: 47 that can be used as the sta011 antigen or to prepare it include, but are not limited to, SEQ ID NOs: 213, 214 and 215 with various Ile / Val / Leu substitutions.</p><p num="0167"> Sta011 can exist as a monomer or oligomer, Ca⁺⁺Ions are favorable for oligomerization. The present invention can use Sta011 monomers and / or oligomers.</p><p num="0168"> (sta012) The "sta012" antigen has been annotated as a "leader-bearing protein". In the NCTC8325 strain, sta012 is SAOUHSC_00106 and has the amino acid sequence of SEQ ID NO: 48 (GI: 88193919).</p><p num="0169"> A useful sta012 antigen can elicit an antibody that recognizes SEQ ID NO: 48 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 48 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 48 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta012 proteins contain variants of SEQ ID NO: 48. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 48. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 48 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 48 It holds one epitope. The first 21 N-terminal amino acids of SEQ ID NO: 48 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0170"> (sta013) The "sta013" antigen is annotated as a "polygamma-glutamic acid capsule biosynthetic protein". In the NCTC8325 strain, sta013 is SAOUHSC_00107 and has the amino acid sequence of SEQ ID NO: 49 (GI: 88193920).</p><p num="0171"> A useful sta013 antigen can elicit an antibody that recognizes SEQ ID NO: 49 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 49 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 49 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta013 proteins contain variants of SEQ ID NO: 49. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 49. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 49 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 49 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0172"> (sta014) The "sta014" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta014 is SAOUHSC_00137 and has the amino acid sequence of SEQ ID NO: 50 (GI: 88193950).</p><p num="0173"> A useful sta014 antigen can elicit an antibody that recognizes SEQ ID NO: 50 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 50 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 50 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta014 proteins contain variants of SEQ ID NO: 50. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 50. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 50 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 50 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 50 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0174"> (sta015) The "sta015" antigen is annotated as "extracellular solute-binding protein; RGD-containing lipoprotein". In the NCTC8325 strain, sta015 is SAOUHSC_00170 and has the amino acid sequence of SEQ ID NO: 51 (GI: 88193980).</p><p num="0175"> A useful sta015 antigen can elicit an antibody that recognizes SEQ ID NO: 51 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 51 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 51 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta015 proteins include variants of SEQ ID NO: 51. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 51. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 51 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 51 It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 51 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0176"> (sta016) The "sta016" antigen is annotated as "gamma-glutamyl transpeptidase". In the NCTC8325 strain, sta016 is SAOUHSC_00171 and has the amino acid sequence of SEQ ID NO: 52 (GI: 88193981).</p><p num="0177"> A useful sta016 antigen can elicit an antibody that recognizes SEQ ID NO: 52 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 52 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 52 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta016 proteins contain variants of SEQ ID NO: 52. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 52. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 52 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 52 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0178"> (sta017) The "sta017" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta017 is SAOUHSC_00186 and has the amino acid sequence of SEQ ID NO: 53 (GI: 88193996).</p><p num="0179"> A useful sta017 antigen can elicit an antibody that recognizes SEQ ID NO: 53 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 53 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 53 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta017 proteins include variants of SEQ ID NO: 53. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 53. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 53 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 53 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 53 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0180"> (sta018) The "sta018" antigen is annotated as an "extracellular solute-binding protein". In the NCTC8325 strain, sta018 is SAOUHSC_00201 and has the amino acid sequence of SEQ ID NO: 54 (GI: 88194011).</p><p num="0181"> A useful sta018 antigen can elicit an antibody that recognizes SEQ ID NO: 54 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 54 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 54 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta018 proteins include variants of SEQ ID NO: 54. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 54. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 54 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 54 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0182"> (sta019) The "sta019" antigen has been annotated as a "peptidoglycan hydrolase". In the NCTC8325 strain, sta019 is SAOUHSC_00248 and has the amino acid sequence of SEQ ID NO: 55 (GI: 88194055). In the Newman strain, this is nwmn_0210 (GI: 151220422).</p><p num="0183"> A useful sta019 antigen can elicit an antibody that recognizes SEQ ID NO: 55 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 55 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 55 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta019 proteins include variants of SEQ ID NO: 55. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 55. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 55 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 55 It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 55 can be conveniently removed. Other fragments have one or more protein domains removed. Useful fragments are SEQ ID NOs: 228 and 229.</p><p num="0184"> Since Sta019 does not adsorb well to the aluminum hydroxide adjuvant, Sta019 present in the composition may not be adsorbed or may be adsorbed to an alternative adjuvant, such as aluminum phosphate.</p><p num="0185"> (sta020) The "sta020" antigen has been annotated as an "exported protein". In the NCTC8325 strain, sta020 is SAOUHSC_00253 and has the amino acid sequence of SEQ ID NO: 56 (GI: 88194059).</p><p num="0186"> A useful sta020 antigen can elicit an antibody that recognizes SEQ ID NO: 56 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 56 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 56 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta020 proteins include variants of SEQ ID NO: 56. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 56. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 56 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 56 It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 56 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0187"> (sta021) The "sta021" antigen is annotated as a "secretory antigen SsaA-like protein". In the NCTC8325 strain, sta021 is SAOUHSC_00256 and has the amino acid sequence of SEQ ID NO: 57 (GI: 88194062).</p><p num="0188"> A useful sta021 antigen can elicit an antibody that recognizes SEQ ID NO: 57 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 57 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 57 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta021 proteins contain variants of SEQ ID NO: 57. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 57. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 57 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 57. It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 57 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0189"> (sta022) The "sta022" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta022 is SAOUHSC_00279 and has the amino acid sequence of SEQ ID NO: 58 (GI: 88194083).</p><p num="0190"> A useful sta022 antigen can elicit an antibody that recognizes SEQ ID NO: 58 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 58 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 58 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta022 proteins contain variants of SEQ ID NO: 58. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 58. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 58 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 58 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 58 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0191"> (sta023) The "sta023" antigen has been annotated as the "5'-nucleotidase; lipoprotein e (P4) family". In the NCTC8325 strain, sta023 is SAOUHSC_00284 and has the amino acid sequence of SEQ ID NO: 59 (GI: 88194087).</p><p num="0192"> A useful sta023 antigen can elicit an antibody that recognizes SEQ ID NO: 59 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 59 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 59 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta023 proteins contain variants of SEQ ID NO: 59. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 59. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 59 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 59 It holds one epitope. The first 31 N-terminal amino acids of SEQ ID NO: 59 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0193"> (sta024) The "sta024" antigen has been annotated as a "lipase precursor". In the NCTC8325 strain, sta024 is SAOUHSC_00300 and has the amino acid sequence of SEQ ID NO: 60 (GI: 88194101).</p><p num="0194"> A useful sta024 antigen can elicit an antibody that recognizes SEQ ID NO: 60 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 60 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 60 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta024 proteins contain variants of SEQ ID NO: 60. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 60. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 60 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 60 It holds one epitope. The first 37 N-terminal amino acids of SEQ ID NO: 60 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0195"> (sta025) The "sta025" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta025 is SAOUHSC_00362 and has the amino acid sequence of SEQ ID NO: 61 (GI: 88194160).</p><p num="0196"> A useful sta025 antigen can elicit an antibody that recognizes SEQ ID NO: 61 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 61 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 61 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta025 proteins contain variants of SEQ ID NO: 61. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 61. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 61 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 61 It holds one epitope. The first 19 N-terminal amino acids of SEQ ID NO: 61 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0197"> (sta026) The "sta026" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta026 is SAOUHSC_00404 and has the amino acid sequence of SEQ ID NO: 62 (GI: 88194198).</p><p num="0198"> A useful sta026 antigen can elicit an antibody that recognizes SEQ ID NO: 62 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 62 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 62 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta026 proteins contain variants of SEQ ID NO: 62. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 62. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 62 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 62 It holds one epitope. The first 22 N-terminal amino acids of SEQ ID NO: 62 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0199"> (sta027) The "sta027" antigen has been annotated as a "presumed lipase". In the NCTC8325 strain, sta027 is SAOUHSC_00661 and has the amino acid sequence of SEQ ID NO: 63 (GI: 88194426).</p><p num="0200"> A useful sta027 antigen can elicit an antibody that recognizes SEQ ID NO: 63 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 63 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 63 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta027 proteins contain variants of SEQ ID NO: 63. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 63. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 63 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 63. It holds one epitope. The first 23 N-terminal amino acids of SEQ ID NO: 63 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0201"> (sta028) The "sta028" antigen is annotated as a "secretory antigen SsaA-like protein". In the NCTC8325 strain, sta028 is SAOUHSC_00671 and has the amino acid sequence of SEQ ID NO: 64 (GI: 88194436). In the Newman strain, this is nwmn_0634 (GI: 151220846).</p><p num="0202"> A useful sta028 antigen can elicit an antibody that recognizes SEQ ID NO: 64 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 64 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 64 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta028 proteins contain variants of SEQ ID NO: 64. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 64. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 64 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 64 It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 64 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0203"> (sta029) The "sta029" antigen has been annotated as a "ferrichrome-binding protein". In the NCTC8325 strain, sta029 is SAOUHSC_00754 and has the amino acid sequence of SEQ ID NO: 65 (GI: 88194518).</p><p num="0204"> A useful sta029 antigen can elicit an antibody that recognizes SEQ ID NO: 65 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 65 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 65 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta029 proteins contain variants of SEQ ID NO: 65. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 65. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 65 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 65 It holds one epitope. The last 25 C-terminal amino acids of SEQ ID NO: 65 can be conveniently removed. The first 19 N-terminal amino acids of SEQ ID NO: 65 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0205"> (sta030) The "sta030" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta030 is SAOUHSC_00808 and has the amino acid sequence of SEQ ID NO: 66 (GI: 88194568).</p><p num="0206"> A useful sta030 antigen can elicit an antibody that recognizes SEQ ID NO: 66 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 66 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 66 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta030 proteins contain variants of SEQ ID NO: 66. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 66. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 66 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 66 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 66 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0207"> (sta031) The "sta031" antigen has been annotated as a "5'-nucleotidase family protein". In the NCTC8325 strain, sta031 is SAOUHSC_00860 and has the amino acid sequence of SEQ ID NO: 67 (GI: 88194617).</p><p num="0208"> A useful sta031 antigen can elicit an antibody that recognizes SEQ ID NO: 67 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 67 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 67 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta031 proteins contain variants of SEQ ID NO: 67. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 67. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 67 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 67 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0209"> (sta032) The "sta032" antigen is annotated as "serine protease HtrA". In the NCTC8325 strain, sta032 is SAOUHSC_00958 and has the amino acid sequence of SEQ ID NO: 68 (GI: 88194715).</p><p num="0210"> A useful sta032 antigen can elicit an antibody that recognizes SEQ ID NO: 68 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 68 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 68 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta032 proteins contain variants of SEQ ID NO: 68. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 68. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 68 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 68 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0211"> (sta033) The "sta033" antigen has been annotated as a "cysteine protease precursor". In the NCTC8325 strain, sta033 is SAOUHSC_00987 and has the amino acid sequence of SEQ ID NO: 69 (GI: 88194744).</p><p num="0212"> A useful sta033 antigen can elicit an antibody that recognizes SEQ ID NO: 69 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 69 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 69 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta033 proteins contain variants of SEQ ID NO: 69. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 69. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 69 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 69 It holds one epitope. The first 29 N-terminal amino acids of SEQ ID NO: 69 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0213"> (sta034) The "sta034" antigen has been annotated as a "glutamyl endopeptidase precursor". In the NCTC8325 strain, sta034 is SAOUHSC_00988 and has the amino acid sequence of SEQ ID NO: 70 (GI: 88194745).</p><p num="0214"> A useful sta034 antigen can elicit an antibody that recognizes SEQ ID NO: 70 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 70 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 70 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta034 proteins contain variants of SEQ ID NO: 70. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 70. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 70 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 70 It holds one epitope. The first 29 N-terminal amino acids of SEQ ID NO: 70 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0215"> (sta035) The "sta035" antigen is annotated as the "fmt protein". In the NCTC8325 strain, sta035 is SAOUHSC_00998 and has the amino acid sequence of SEQ ID NO: 71 (GI: 88194754).</p><p num="0216"> A useful sta035 antigen can elicit an antibody that recognizes SEQ ID NO: 71 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 71 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 71 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta035 proteins contain variants of SEQ ID NO: 71. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 71. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 71 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 71. It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 71 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0217"> (sta036) The "sta036" antigen has been annotated as an "iron regulatory protein with a leader". In the NCTC8325 strain, sta036 is SAOUHSC_01084 and has the amino acid sequence of SEQ ID NO: 72 (GI: 88194831).</p><p num="0218"> A useful sta036 antigen can elicit an antibody that recognizes SEQ ID NO: 72 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 72 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 72 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta036 proteins contain variants of SEQ ID NO: 72. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 72. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 72 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 72 It holds one epitope. The last 27 C-terminal amino acids of SEQ ID NO: 72 can be conveniently removed. The first 32 N-terminal amino acids of SEQ ID NO: 72 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0219"> (sta037) The "sta037" antigen is annotated as an "iron ABC transporter; iron binding protein IsdE". In the NCTC8325 strain, sta037 is SAOUHSC_01085 and has the amino acid sequence of SEQ ID NO: 73 (GI: 88194832).</p><p num="0220"> A useful sta037 antigen can elicit an antibody that recognizes SEQ ID NO: 73 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 73 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 73 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta037 proteins contain variants of SEQ ID NO: 73. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 73. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 73 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 73. It holds one epitope. The first 9 N-terminal amino acids of SEQ ID NO: 73 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0221"> (sta038) The "sta038" antigen has been annotated as "NPQTN-specific sortase B". In the NCTC8325 strain, sta038 is SAOUHSC_01088 and has the amino acid sequence of SEQ ID NO: 74 (GI: 88194835).</p><p num="0222"> A useful sta038 antigen can elicit an antibody that recognizes SEQ ID NO: 74 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 74 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 74 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta038 proteins include variants of SEQ ID NO: 74. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 74. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 74 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 74 It holds one epitope. The first 21 N-terminal amino acids of SEQ ID NO: 74 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0223"> (sta039) The "sta039" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta039 is SAOUHSC_01124 and has the amino acid sequence of SEQ ID NO: 75 (GI: 88194868).</p><p num="0224"> A useful sta039 antigen can elicit an antibody that recognizes SEQ ID NO: 75 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 75 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 75 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta039 proteins contain variants of SEQ ID NO: 75. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 75. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 75 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 75 It holds one epitope. The first 22 N-terminal amino acids of SEQ ID NO: 75 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0225"> (sta040) The "sta040" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta040 is SAOUHSC_01125 and has the amino acid sequence of SEQ ID NO: 76 (GI: 88194869). In the Newman strain, this is nwmn_1076 (GI: 151221288).</p><p num="0226"> A useful sta040 antigen can elicit an antibody that recognizes SEQ ID NO: 76 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 76 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 76 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta040 proteins include variants of SEQ ID NO: 76. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 76. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 76 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 76 It holds one epitope. The first 21 N-terminal amino acids of SEQ ID NO: 76 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0227"> (sta041) The "sta041" antigen has been annotated as "fibronectin binding protein A-related". In the NCTC8325 strain, sta041 is SAOUHSC_01175 and has the amino acid sequence of SEQ ID NO: 77 (GI: 88194914).</p><p num="0228"> A useful sta041 antigen can elicit an antibody that recognizes SEQ ID NO: 77 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 77 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 77 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta041 proteins contain variants of SEQ ID NO: 77. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 77. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 77 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 77 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0229"> (sta042) The "sta042" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta042 is SAOUHSC_01180 and has the amino acid sequence of SEQ ID NO: 78 (GI: 88194919).</p><p num="0230"> A useful sta042 antigen can elicit an antibody that recognizes SEQ ID NO: 78 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 78 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 78 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta042 proteins contain variants of SEQ ID NO: 78. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 78. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 78 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 78. It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 78 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0231"> (sta043) The "sta043" antigen is annotated as a "cell wall hydrolase". In the NCTC8325 strain, sta043 is SAOUHSC_01219 and has the amino acid sequence of SEQ ID NO: 79 (GI: 88194955).</p><p num="0232"> A useful sta043 antigen can elicit an antibody that recognizes SEQ ID NO: 79 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 79 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 79 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta043 proteins contain variants of SEQ ID NO: 79. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 79. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 79 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 79 It holds one epitope. The first 38 N-terminal amino acids of SEQ ID NO: 79 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0233"> (sta044) The "sta044" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta044 is SAOUHSC_01508 and has the amino acid sequence of SEQ ID NO: 80 (GI: 88195223).</p><p num="0234"> A useful sta044 antigen can elicit an antibody that recognizes SEQ ID NO: 80 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 80 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 80 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta044 proteins contain variants of SEQ ID NO: 80. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 80. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 80 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 80 It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 80 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0235"> (sta045) The "sta045" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta045 is SAOUHSC_01627 and has the amino acid sequence of SEQ ID NO: 81 (GI: 88195337).</p><p num="0236"> A useful sta045 antigen can elicit an antibody that recognizes SEQ ID NO: 81 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 81 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 81 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta045 proteins contain variants of SEQ ID NO: 81. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 81. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 81 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 81 It holds one epitope. The first 16 N-terminal amino acids of SEQ ID NO: 81 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0237"> (sta046) The "sta046" antigen is annotated as an "Excalibur protein". In the NCTC8325 strain, sta046 is SAOUHSC_01918 and has the amino acid sequence of SEQ ID NO: 82 (GI: 88195613).</p><p num="0238"> A useful sta046 antigen can elicit an antibody that recognizes SEQ ID NO: 82 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 82 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 82 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta046 proteins contain variants of SEQ ID NO: 82. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 82. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 82 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 82 It holds one epitope. The first 53 N-terminal amino acids of SEQ ID NO: 82 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0239"> (sta047) The "sta047" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta047 is SAOUHSC_01920 and has the amino acid sequence of SEQ ID NO: 83 (GI: 88195615).</p><p num="0240"> A useful sta047 antigen can elicit an antibody that recognizes SEQ ID NO: 83 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 83 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 83 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta047 proteins contain variants of SEQ ID NO: 83. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 83. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 83 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 83. It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 83 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0241"> (sta048) The "sta048" antigen is annotated as an "intracellular serine protease". In the NCTC8325 strain, sta048 is SAOUHSC_01949 and has the amino acid sequence of SEQ ID NO: 84 (GI: 88195642).</p><p num="0242"> A useful sta048 antigen can elicit an antibody that recognizes SEQ ID NO: 84 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 84 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 84 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta048 proteins contain variants of SEQ ID NO: 84. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 84. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 84 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 84 It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 84 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0243"> (sta049) The "sta049" antigen is annotated as "protein transport protein PrsA". In the NCTC8325 strain, sta049 is SAOUHSC_01972 and has the amino acid sequence of SEQ ID NO: 85 (GI: 88195663). In the Newman strain, this is nwmn_1733 (GI: 151221945).</p><p num="0244"> A useful sta049 antigen can elicit an antibody that recognizes SEQ ID NO: 85 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 85 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 85 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta049 proteins contain variants of SEQ ID NO: 85. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 85. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 85 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 85 It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 85 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0245"> (sta050) The "sta050" antigen is annotated as a "stahopine thiol proteinase". In the NCTC8325 strain, sta050 is SAOUHSC_02127 and has the amino acid sequence of SEQ ID NO: 86 (GI: 88195808).</p><p num="0246"> A useful sta050 antigen can elicit an antibody that recognizes SEQ ID NO: 86 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 86 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 86 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta050 proteins contain variants of SEQ ID NO: 86. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 86. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 86 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 86 It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 86 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0247"> (sta051) The "sta051" antigen has been annotated as a "leader-bearing protein". In the NCTC8325 strain, sta051 is SAOUHSC_02147 and has the amino acid sequence of SEQ ID NO: 87 (GI: 88195827).</p><p num="0248"> A useful sta051 antigen can elicit an antibody that recognizes SEQ ID NO: 87 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 87 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 87 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta051 proteins contain variants of SEQ ID NO: 87. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 87. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 87 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 87 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 87 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0249"> (sta052) The "sta052" antigen is annotated as "ferric hydroxamic acid receptor 1". In the NCTC8325 strain, sta052 is SAOUHSC_02246 and has the amino acid sequence of SEQ ID NO: 88 (GI: 88195918).</p><p num="0250"> A useful sta052 antigen can elicit an antibody that recognizes SEQ ID NO: 88 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 88 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 88 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta052 proteins contain variants of SEQ ID NO: 88. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 88. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 88 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 88. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 88 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0251"> (sta053) The "sta053" antigen has been annotated as a "srdH family protein". In the NCTC8325 strain, sta053 is SAOUHSC_02257 and has the amino acid sequence of SEQ ID NO: 89 (GI: 88195928).</p><p num="0252"> A useful sta053 antigen can elicit an antibody that recognizes SEQ ID NO: 89 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 89 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 89 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta053 proteins contain variants of SEQ ID NO: 89. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 89. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 89 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 89 It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 89 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0253"> (sta054) The "sta054" antigen has been annotated as a "presumed transglycosylase isaA precursor". In the NCTC8325 strain, sta054 is SAOUHSC_02333 and has the amino acid sequence of SEQ ID NO: 90 (GI: 88195999).</p><p num="0254"> A useful sta054 antigen can elicit an antibody that recognizes SEQ ID NO: 90 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 90 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 90 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta054 proteins contain variants of SEQ ID NO: 90. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 90. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 90 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 90 It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 90 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0255"> (sta055) The "sta055" antigen is annotated as a "surface hydrolase". In the NCTC8325 strain, sta055 is SAOUHSC_02448 and has the amino acid sequence of SEQ ID NO: 91 (GI: 88196100).</p><p num="0256"> A useful sta055 antigen can elicit an antibody that recognizes SEQ ID NO: 91 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 91 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 91 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta055 proteins include variants of SEQ ID NO: 91. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 91. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 91 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 91 It holds one epitope. The first 31 N-terminal amino acids of SEQ ID NO: 91 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0257"> (sta056) The "sta056" antigen is annotated as "hyaluronic acid lyase". In the NCTC8325 strain, sta056 is SAOUHSC_02463 and has the amino acid sequence of SEQ ID NO: 92 (GI: 88196115).</p><p num="0258"> A useful sta056 antigen can elicit an antibody that recognizes SEQ ID NO: 92 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 92 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 92 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta056 proteins contain variants of SEQ ID NO: 92. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 92. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 92 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 92. It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 92 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0259"> (sta057) The "sta057" antigen is annotated as "secretory antigen precursor SsaA". In the NCTC8325 strain, sta057 is SAOUHSC_02576 and has the amino acid sequence of SEQ ID NO: 93 (GI: 88196220). In the Newman strain, this is nwmn_2203 (GI: 151222415).</p><p num="0260"> A useful sta057 antigen can elicit an antibody that recognizes SEQ ID NO: 93 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 93 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 93 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta057 proteins contain variants of SEQ ID NO: 93. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 93. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 93 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 93. It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 93 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0261"> (sta058) The "sta058" antigen is annotated as "Zn-binding lipoprotein adcA-like". In the NCTC8325 strain, sta058 is SAOUHSC_02690 and has the amino acid sequence of SEQ ID NO: 94 (GI: 88196330).</p><p num="0262"> A useful sta058 antigen can elicit an antibody that recognizes SEQ ID NO: 94 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 94 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 94 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta058 proteins contain variants of SEQ ID NO: 94. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 94. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 94 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 94. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 94 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0263"> (sta059) The "sta059" antigen is annotated as the "gamma hemolysin h-gamma-ii subunit". In the NCTC8325 strain, sta059 is SAOUHSC_02708 and has the amino acid sequence of SEQ ID NO: 95 (GI: 88196348).</p><p num="0264"> A useful sta059 antigen can elicit an antibody that recognizes SEQ ID NO: 95 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 95 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 95 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta059 proteins contain variants of SEQ ID NO: 95. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 95. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 95 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 95 It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 95 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0265"> (sta060) The "sta060" antigen is annotated as a "peptide ABC transporter; peptide binding protein". In the NCTC8325 strain, sta060 is SAOUHSC_02767 and has the amino acid sequence of SEQ ID NO: 96 (GI: 88196403).</p><p num="0266"> A useful sta060 antigen can elicit an antibody that recognizes SEQ ID NO: 96 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 96 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 96 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta060 proteins contain variants of SEQ ID NO: 96. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 96. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 96 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 96 It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 96 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0267"> (sta061) The "sta061" antigen has been annotated as a "leader-bearing protein". In the NCTC8325 strain, sta061 is SAOUHSC_02783 and has the amino acid sequence of SEQ ID NO: 97 (GI: 88196419).</p><p num="0268"> A useful sta061 antigen can elicit an antibody that recognizes SEQ ID NO: 97 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 97 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 97 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta061 proteins contain variants of SEQ ID NO: 97. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 97. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 97 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 97 It holds one epitope. The first 21 N-terminal amino acids of SEQ ID NO: 97 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0269"> (sta062) The "sta062" antigen has been annotated as a "leader-bearing protein". In the NCTC8325 strain, sta062 is SAOUHSC_02788 and has the amino acid sequence of SEQ ID NO: 98 (GI: 88196424).</p><p num="0270"> A useful sta062 antigen can elicit an antibody that recognizes SEQ ID NO: 98 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 98 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 98 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta062 proteins contain variants of SEQ ID NO: 98. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 98. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 98 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 98 It holds one epitope. The first 22 N-terminal amino acids of SEQ ID NO: 98 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0271"> (sta063) The "sta063" antigen has been annotated as "aureolysin". In the NCTC8325 strain, sta063 is SAOUHSC_02971 and has the amino acid sequence of SEQ ID NO: 99 (GI: 88196592).</p><p num="0272"> A useful sta063 antigen can elicit an antibody that recognizes SEQ ID NO: 99 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 99 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 99 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta063 proteins contain variants of SEQ ID NO: 99. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 99. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 99 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 99 It holds one epitope. The first 16 N-terminal amino acids of SEQ ID NO: 99 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0273"> (sta064) The "sta064" antigen is annotated as "lipase". In the NCTC8325 strain, sta064 is SAOUHSC_03006 and has the amino acid sequence of SEQ ID NO: 100 (GI: 88196625). In the Newman strain, this is nwmn_2569 (GI: 151222781).</p><p num="0274"> A useful sta064 antigen can elicit an antibody that recognizes SEQ ID NO: 100 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 100 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 100 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta064 proteins contain variants of SEQ ID NO: 100. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 100. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 100 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 100 It holds one epitope. The first 34 N-terminal amino acids of SEQ ID NO: 100 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0275"> (sta065) The "sta065" antigen has been annotated as a "1-phosphatidylinositol phosphodiesterase precursor". In the NCTC8325 strain, sta065 is SAOUHSC_00051 and has the amino acid sequence of SEQ ID NO: 101 (GI: 88193871).</p><p num="0276"> A useful sta065 antigen can elicit an antibody that recognizes SEQ ID NO: 101 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 101 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 101 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta065 proteins include variants of SEQ ID NO: 101. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 101. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 101 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 101. It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 101 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0277"> (sta066) The "sta066" antigen is annotated as a "protein". In the NCTC8325 strain, sta066 is SAOUHSC_00172 and has the amino acid sequence of SEQ ID NO: 102 (GI: 88193982).</p><p num="0278"> A useful sta066 antigen can elicit an antibody that recognizes SEQ ID NO: 102 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 102 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 102 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta066 proteins include variants of SEQ ID NO: 102. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 102. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 102 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 102. It holds one epitope. The first 21 N-terminal amino acids of SEQ ID NO: 102 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0279"> (sta067) The "sta067" antigen has been annotated as a "bacterial extracellular solute-binding protein". In the NCTC8325 strain, sta067 is SAOUHSC_00176 and has the amino acid sequence of SEQ ID NO: 103 (GI: 88193986).</p><p num="0280"> A useful sta067 antigen can elicit an antibody that recognizes SEQ ID NO: 103 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 103 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 103 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta067 proteins contain variants of SEQ ID NO: 103. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 103. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 103 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 103. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 103 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0281"> (sta068) The "sta068" antigen is annotated as "iron permase FTR1". In the NCTC8325 strain, sta068 is SAOUHSC_00327 and has the amino acid sequence of SEQ ID NO: 104 (GI: 88194127).</p><p num="0282"> A useful sta068 antigen can elicit an antibody that recognizes SEQ ID NO: 104 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 104 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 104 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta068 proteins contain variants of SEQ ID NO: 104. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 104. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 104 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 104. It holds one epitope. The last 20 C-terminal amino acids of SEQ ID NO: 104 can be conveniently removed. The first 14 N-terminal amino acids of SEQ ID NO: 104 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0283"> (sta069) The "sta069" antigen has been annotated as a "autolytic precursor". In the NCTC8325 strain, sta069 is SAOUHSC_00427 and has the amino acid sequence of SEQ ID NO: 105 (GI: 88194219).</p><p num="0284"> A useful sta069 antigen can elicit an antibody that recognizes SEQ ID NO: 105 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 105 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 105 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta069 proteins contain variants of SEQ ID NO: 105. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 105. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 105 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 105. It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 105 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0285"> (sta070) The "sta070" antigen is annotated as an "immunogenic secretory precursor-like protein (cleaved)". In the NCTC8325 strain, sta070 is SAOUHSC_00773 and has the amino acid sequence of SEQ ID NO: 106 (GI: 88194535).</p><p num="0286"> A useful sta070 antigen can elicit an antibody that recognizes SEQ ID NO: 106 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 106 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 106 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta070 proteins include variants of SEQ ID NO: 106. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 106. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 106 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 106 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 106 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0287"> (sta071) The "sta071" antigen is annotated as "hemolysin". In the NCTC8325 strain, sta071 is SAOUHSC_00854 and has the amino acid sequence of SEQ ID NO: 107 (GI: 88194612).</p><p num="0288"> A useful sta071 antigen can elicit an antibody that recognizes SEQ ID NO: 107 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 107 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 107 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta071 proteins contain variants of SEQ ID NO: 107. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 107. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 107 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 107 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 107 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0289"> (sta072) The "sta072" antigen is annotated as an "extramembrane protein". In the NCTC8325 strain, sta072 is SAOUHSC_00872 and has the amino acid sequence of SEQ ID NO: 108 (GI: 88194629).</p><p num="0290"> A useful sta072 antigen can elicit an antibody that recognizes SEQ ID NO: 108 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 108 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 108 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta072 proteins contain variants of SEQ ID NO: 108. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 108. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 108 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 108 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 108 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0291"> (sta073) The "sta073" antigen has been annotated as a "bifunctional autolytic precursor". In the NCTC8325 strain, sta073 is SAOUHSC_00994 and has the amino acid sequence of SEQ ID NO: 109 (GI: 88194750). In the Newman strain, this is nwmn_0922 (GI: 151221134). Proteomics analysis reveals that this protein is secreted or exposed to the surface.</p><p num="0292"> A useful sta073 antigen can elicit an antibody that recognizes SEQ ID NO: 109 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 109 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 109 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta073 proteins contain variants of SEQ ID NO: 109. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 109. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 109 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 109 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 109 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0293"> The Sta073 antigen can be usefully included in the composition in combination with Sta112 [74].</p><p num="0294"> Since Sta073 does not adsorb well to the aluminum hydroxide adjuvant, Sta073 present in the composition may not be adsorbed or may be adsorbed to an alternative adjuvant such as aluminum phosphate.</p><p num="0295"> (sta074) The "sta074" antigen has been annotated as an "essential factor for methicillin resistance". In the NCTC8325 strain, sta074 is SAOUHSC_01220 and has the amino acid sequence of SEQ ID NO: 110 (GI: 88194956).</p><p num="0296"> A useful sta074 antigen can elicit an antibody that recognizes SEQ ID NO: 110 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 110 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 110 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta074 proteins contain variants of SEQ ID NO: 110. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 110. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 110 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 110 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0297"> (sta075) The "sta075" antigen is annotated as "insulin; peptidase family M16". In the NCTC8325 strain, sta075 is SAOUHSC_01256 and has the amino acid sequence of SEQ ID NO: 111 (GI: 88194989).</p><p num="0298"> A useful sta075 antigen can elicit an antibody that recognizes SEQ ID NO: 111 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 111 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 111 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta075 proteins contain variants of SEQ ID NO: 111. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 111. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 111 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 111 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0299"> (sta076) The "sta076" antigen is annotated as a "hydrolase". In the NCTC8325 strain, sta076 is SAOUHSC_01263 and has the amino acid sequence of SEQ ID NO: 112 (GI: 88194996).</p><p num="0300"> A useful sta076 antigen can elicit an antibody that recognizes SEQ ID NO: 112 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 112 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 112 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta076 proteins contain variants of SEQ ID NO: 112. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 112. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 112 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 112 It holds one epitope. The first 24 N-terminal amino acids of SEQ ID NO: 112 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0301"> (sta077) The "sta077" antigen is annotated as a "protein". In the NCTC8325 strain, sta077 is SAOUHSC_01317 and has the amino acid sequence of SEQ ID NO: 113 (GI: 88195047). Proteomics analysis reveals that this protein is secreted or exposed to the surface.</p><p num="0302"> A useful sta077 antigen can elicit an antibody that recognizes SEQ ID NO: 113 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 113 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 113 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta077 proteins contain variants of SEQ ID NO: 113. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 113. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 113 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 113. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 113 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0303"> (sta078) The "sta078" antigen has been annotated as a "FtsK / SpoIIIE family protein". In the NCTC8325 strain, sta078 is SAOUHSC_01857 and has the amino acid sequence of SEQ ID NO: 114 (GI: 88195555).</p><p num="0304"> A useful sta078 antigen can elicit an antibody that recognizes SEQ ID NO: 114 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 114 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 114 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta078 proteins contain variants of SEQ ID NO: 114. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 114. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 114 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 114 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0305"> (sta079) The "sta079" antigen is annotated as "serine protease SplF". In the NCTC8325 strain, sta079 is SAOUHSC_01935 and has the amino acid sequence of SEQ ID NO: 115 (GI: 88195630).</p><p num="0306"> A useful sta079 antigen can elicit an antibody that recognizes SEQ ID NO: 115 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 115 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 115 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta079 proteins contain variants of SEQ ID NO: 115. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 115. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 115 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 115 It holds one epitope. The first 36 N-terminal amino acids of SEQ ID NO: 115 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0307"> (sta080) The "sta080" antigen is annotated as "serine protease SplE". In the NCTC8325 strain, sta080 is SAOUHSC_01936 and has the amino acid sequence of SEQ ID NO: 116 (GI: 88195631).</p><p num="0308"> A useful sta080 antigen can elicit an antibody that recognizes SEQ ID NO: 116 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 116 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 116 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta080 proteins include variants of SEQ ID NO: 116. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 116. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 116 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 116 It holds one epitope. The first 36 N-terminal amino acids of SEQ ID NO: 116 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0309"> (sta081) The "sta081" antigen is annotated as "serine protease SplD (EC: 3.4.21.19)". In the NCTC8325 strain, sta081 is SAOUHSC_01938 and has the amino acid sequence of SEQ ID NO: 170 (GI: 88195633).</p><p num="0310"> A useful sta081 antigen can elicit an antibody that recognizes SEQ ID NO: 170 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 170 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 170 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta081 proteins contain variants of SEQ ID NO: 170. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 170. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 170 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 170 It holds one epitope. The first 36 N-terminal amino acids of SEQ ID NO: 170 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0311"> (sta082) The "sta082" antigen is annotated as "serine protease SplC". In the NCTC8325 strain, sta082 is SAOUHSC_01939 and has the amino acid sequence of SEQ ID NO: 117 (GI: 88195634).</p><p num="0312"> A useful sta082 antigen can elicit an antibody that recognizes SEQ ID NO: 117 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 117 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 117 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta082 proteins contain variants of SEQ ID NO: 117. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 117. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 117 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 117 It holds one epitope. The first 36 N-terminal amino acids of SEQ ID NO: 117 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0313"> (sta083) The "sta083" antigen is annotated as "serine protease SplB". In the NCTC8325 strain, sta083 is SAOUHSC_01941 and has the amino acid sequence of SEQ ID NO: 118 (GI: 88195635).</p><p num="0314"> A useful sta083 antigen can elicit an antibody that recognizes SEQ ID NO: 118 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 118 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 118 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta083 proteins contain variants of SEQ ID NO: 118. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 118. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 118 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 118 It holds one epitope. The first 36 N-terminal amino acids of SEQ ID NO: 118 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0315"> (sta084) The "sta084" antigen is annotated as "serine protease SplA". In the NCTC8325 strain, sta084 is SAOUHSC_01942 and has the amino acid sequence of SEQ ID NO: 119 (GI: 88195636).</p><p num="0316"> A useful sta084 antigen can elicit an antibody that recognizes SEQ ID NO: 119 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 119 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 119 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta084 proteins contain variants of SEQ ID NO: 119. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 119. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 119 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 119. It holds one epitope. The first 35 N-terminal amino acids of SEQ ID NO: 119 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0317"> (sta085) The "sta085" antigen has been annotated as a "staphylokinase precursor". In the NCTC8325 strain, sta085 is SAOUHSC_02171 and has the amino acid sequence of SEQ ID NO: 120 (GI: 88195848).</p><p num="0318"> A useful sta085 antigen can elicit an antibody that recognizes SEQ ID NO: 120 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 120 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 120 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta085 proteins contain variants of SEQ ID NO: 120. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 120. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 120 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 120 It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 120 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0319"> (sta086) The "sta086" antigen is annotated as an "OxaA-like protein". In the NCTC8325 strain, sta086 is SAOUHSC_02327 and has the amino acid sequence of SEQ ID NO: 121 (GI: 88195993).</p><p num="0320"> A useful sta086 antigen can elicit an antibody that recognizes SEQ ID NO: 121 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 121 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 121 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta086 proteins contain variants of SEQ ID NO: 121. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 121. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 121 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 121 It holds one epitope. The first 19 N-terminal amino acids of SEQ ID NO: 121 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0321"> (sta087) The "sta087" antigen is annotated as "teicoplanin resistant protein TcaA". In the NCTC8325 strain, sta087 is SAOUHSC_02635 and has the amino acid sequence of SEQ ID NO: 122 (GI: 88196276).</p><p num="0322"> A useful sta087 antigen can elicit an antibody that recognizes SEQ ID NO: 122 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 122 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 122 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta087 proteins contain variants of SEQ ID NO: 122. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 122. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 122 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 122. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0323"> (sta088) The "sta088" antigen is annotated as "esterase". In the NCTC8325 strain, sta088 is SAOUHSC_02844 and has the amino acid sequence of SEQ ID NO: 123 (GI: 88196477).</p><p num="0324"> A useful sta088 antigen can elicit an antibody that recognizes SEQ ID NO: 123 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 123 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 123 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta088 proteins contain variants of SEQ ID NO: 123. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 123. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 123 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 123 It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 123 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0325"> (sta089) The "sta089" antigen has been annotated as a "LysM domain protein". In the NCTC8325 strain, sta089 is SAOUHSC_02855 and has the amino acid sequence of SEQ ID NO: 124 (GI: 88196486).</p><p num="0326"> A useful sta089 antigen can elicit an antibody that recognizes SEQ ID NO: 124 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 124 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 124 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta089 proteins contain variants of SEQ ID NO: 124. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 124. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 124 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 124. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 124 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0327"> (sta090) The "sta090" antigen is annotated as a "LysM domain protein". In the NCTC8325 strain, sta090 is SAOUHSC_02883 and has the amino acid sequence of SEQ ID NO: 125 (GI: 88196512).</p><p num="0328"> A useful sta090 antigen can elicit an antibody that recognizes SEQ ID NO: 125 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 125 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 125 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta090 proteins include variants of SEQ ID NO: 125. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 125. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 125 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 125 It holds one epitope. The first 26 N-terminal amino acids of SEQ ID NO: 125 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0329"> (sta091) The "sta091" antigen is annotated as a "lipoprotein". In the NCTC8325 strain, sta091 is SAOUHSC_00685 and has the amino acid sequence of SEQ ID NO: 126 (GI: 88194450).</p><p num="0330"> A useful sta091 antigen can elicit an antibody that recognizes SEQ ID NO: 126 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 126 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 126 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta091 proteins contain variants of SEQ ID NO: 126. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 126. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 126 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 126 It holds one epitope. The first 15 N-terminal amino acids of SEQ ID NO: 126 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0331"> (sta092) The "sta092" antigen has been annotated as a "M23 / M37 peptidase domain protein". In the NCTC8325 strain, sta092 is SAOUHSC_00174 and has the amino acid sequence of SEQ ID NO: 127 (GI: 88193984).</p><p num="0332"> A useful sta092 antigen can elicit an antibody that recognizes SEQ ID NO: 127 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 127 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 127 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta092 proteins contain variants of SEQ ID NO: 127. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 127. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 127 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 127. It holds one epitope. The first 25 N-terminal amino acids of SEQ ID NO: 127 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0333"> (sta093) The "sta093" antigen is annotated as a "protein". In the NCTC8325 strain, sta093 is SAOUHSC_01854 and has the amino acid sequence of SEQ ID NO: 128 (GI: 88195552).</p><p num="0334"> A useful sta093 antigen can elicit an antibody that recognizes SEQ ID NO: 128 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 128 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 128 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta093 proteins contain variants of SEQ ID NO: 128. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 128. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 128 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 128 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0335"> (sta094) The "sta094" antigen is annotated as a "protein". In the NCTC8325 strain, sta094 is SAOUHSC_01512 and has the amino acid sequence of SEQ ID NO: 129 (GI: 88195226).</p><p num="0336"> A useful sta094 antigen can elicit an antibody that recognizes SEQ ID NO: 129 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 129 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 129 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta094 proteins contain variants of SEQ ID NO: 129. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 129. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 129 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 129. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 129 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0337"> (sta095) The "sta095" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta095 is SAOUHSC_00383 and has the amino acid sequence of SEQ ID NO: 130 (GI: 88194180). In the Newman strain, this is nwmn_0388 (GI: 151220600).</p><p num="0338"> A useful sta095 antigen can elicit an antibody that recognizes SEQ ID NO: 130 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 130 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 130 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta095 proteins contain variants of SEQ ID NO: 130. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 130. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 130 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 130 It holds one epitope. The first 32 N-terminal amino acids of SEQ ID NO: 130 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0339"> (sta096) The "sta096" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta096 is SAOUHSC_00384 and has the amino acid sequence of SEQ ID NO: 131 (GI: 88194181).</p><p num="0340"> A useful sta096 antigen can elicit an antibody that recognizes SEQ ID NO: 131 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 131 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 131 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta096 proteins contain variants of SEQ ID NO: 131. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 131. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 131 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 131. It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 131 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0341"> (sta097) The "sta097" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta097 is SAOUHSC_00386 and has the amino acid sequence of SEQ ID NO: 132 (GI: 88194182).</p><p num="0342"> A useful sta097 antigen can elicit an antibody that recognizes SEQ ID NO: 132 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 132 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 132 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta097 proteins include variants of SEQ ID NO: 132. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 132. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 132 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 132 It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 132 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0343"> (sta098) The "sta098" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta098 is SAOUHSC_00389 and has the amino acid sequence of SEQ ID NO: 133 (GI: 88194184). In the Newman strain, this is nwmn_0391 (GI: 151220603).</p><p num="0344"> A useful sta098 antigen can elicit an antibody that recognizes SEQ ID NO: 133 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 133 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 133 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta098 proteins contain variants of SEQ ID NO: 133. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 133. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 133 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 133. It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 133 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0345"> (sta099) The "sta099" antigen is annotated as "superantigen-like protein 5". In the NCTC8325 strain, sta099 is SAOUHSC_00390 and has the amino acid sequence of SEQ ID NO: 134 (GI: 88194185).</p><p num="0346"> A useful sta099 antigen can elicit an antibody that recognizes SEQ ID NO: 134 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 134 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 134 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta099 proteins contain variants of SEQ ID NO: 134. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 134. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 134 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 134 It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 134 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0347"> (sta100) The "sta100" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta100 is SAOUHSC_00391 and has the amino acid sequence of SEQ ID NO: 135 (GI: 88194186).</p><p num="0348"> A useful sta100 antigen can elicit an antibody that recognizes SEQ ID NO: 135 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 135 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 135 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta100 proteins include variants of SEQ ID NO: 135. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 135. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 135 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 135. It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 135 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0349"> (sta101) The "sta101" antigen is annotated as "superantigen-like protein 7". In the NCTC8325 strain, sta101 is SAOUHSC_00392 and has the amino acid sequence of SEQ ID NO: 136 (GI: 88194187). In the Newman strain, this is nwmn_0394 (GI: 151220606).</p><p num="0350"> A useful sta101 antigen can elicit an antibody that recognizes SEQ ID NO: 136 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 136 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 136 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta101 proteins contain variants of SEQ ID NO: 136. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 136. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 136 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 136 It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 136 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0351"> (sta102) The "sta102" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta102 is SAOUHSC_00393 and has the amino acid sequence of SEQ ID NO: 137 (GI: 88194188).</p><p num="0352"> A useful sta102 antigen can elicit an antibody that recognizes SEQ ID NO: 137 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 137 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 137 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta102 proteins contain variants of SEQ ID NO: 137. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 137. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 137 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 137. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 137 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0353"> (sta103) The "sta103" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta103 is SAOUHSC_00394 and has the amino acid sequence of SEQ ID NO: 138 (GI: 88194189).</p><p num="0354"> A useful sta103 antigen can elicit an antibody that recognizes SEQ ID NO: 138 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 138 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 138 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta103 proteins contain variants of SEQ ID NO: 138. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 138. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 138 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 138. It holds one epitope. The first 23 N-terminal amino acids of SEQ ID NO: 138 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0355"> (sta104) The "sta104" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta104 is SAOUHSC_00395 and has the amino acid sequence of SEQ ID NO: 139 (GI: 88194190).</p><p num="0356"> A useful sta104 antigen can elicit an antibody that recognizes SEQ ID NO: 139 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 139 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 139 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta104 proteins contain variants of SEQ ID NO: 139. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 139. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 139 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 139. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0357"> (sta105) The "sta105" antigen is annotated as a "superantigen-like protein". In the NCTC8325 strain, sta105 is SAOUHSC_00399 and has the amino acid sequence of SEQ ID NO: 140 (GI: 88194194). In the Newman strain, this is nwmn_0400 (GI: 151220612).</p><p num="0358"> A useful sta105 antigen can elicit an antibody that recognizes SEQ ID NO: 140 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 140 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 140 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta105 proteins include variants of SEQ ID NO: 140. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 140. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 140 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 140 It holds one epitope. The first 30 N-terminal amino acids of SEQ ID NO: 140 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0359"> (sta106) The "sta106" antigen has been annotated as a "virtual protein". In the NCTC8325 strain, sta106 is SAOUHSC_01115 and has the amino acid sequence of SEQ ID NO: 141 (GI: 88194861).</p><p num="0360"> A useful sta106 antigen can elicit an antibody that recognizes SEQ ID NO: 141 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 141 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 141 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta106 proteins include variants of SEQ ID NO: 141. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 141. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 141 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 141 It holds one epitope. The first 16 N-terminal amino acids of SEQ ID NO: 141 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0361"> (sta107) The "sta107" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta107 is SAOUHSC_00354 and has the amino acid sequence of SEQ ID NO: 177 (GI: 88194153).</p><p num="0362"> A useful sta107 antigen can elicit an antibody that recognizes SEQ ID NO: 177 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 177 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 177 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta107 proteins contain variants of SEQ ID NO: 177. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 177. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 177 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 177. It holds one epitope. The first 35 N-terminal amino acids of SEQ ID NO: 177 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0363"> (sta108) The "sta108" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta108 is SAOUHSC_00717 and has the amino acid sequence of SEQ ID NO: 178 (GI: 88194482).</p><p num="0364"> A useful sta108 antigen can elicit an antibody that recognizes SEQ ID NO: 178 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 178 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 178 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta108 proteins contain variants of SEQ ID NO: 178. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 178. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 178 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 178. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 178 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0365"> (sta109) The "sta109" antigen is annotated as "N-acetylmuramoyl-L-alanine amidase". In the NCTC8325 strain, sta109 is SAOUHSC_02979 and has the amino acid sequence of SEQ ID NO: 179 (GI: 88196599).</p><p num="0366"> A useful sta109 antigen can elicit an antibody that recognizes SEQ ID NO: 179 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 179 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 179 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta109 proteins include variants of SEQ ID NO: 179. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 179. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 179 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 179. It holds one epitope. The first 27 N-terminal amino acids of SEQ ID NO: 179 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0367"> (sta110) The "sta110" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta110 is SAOUHSC_01039 and has the amino acid sequence of SEQ ID NO: 180 (GI: 88194791).</p><p num="0368"> A useful sta110 antigen can elicit an antibody that recognizes SEQ ID NO: 180 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 180 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 180 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These sta110 proteins include variants of SEQ ID NO: 180. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 180. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 180 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 180 It holds one epitope. The first 19 N-terminal amino acids of SEQ ID NO: 180 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0369"> (sta111) The "sta111" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta111 is SAOUHSC_01005 and has the amino acid sequence of SEQ ID NO: 181 (GI: 88194760).</p><p num="0370"> A useful sta111 antigen can elicit an antibody that recognizes SEQ ID NO: 181 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 181 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 181 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta111 proteins contain variants of SEQ ID NO: 181. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 181. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 181 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 181. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 181 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0371"> (sta112) The "sta112" antigen has been annotated as a putative "ABC transporter, substrate binding protein". In the NCTC8325 strain, sta112 is SAOUHSC_00634 and has the amino acid sequence of SEQ ID NO: 182 (GI: 88194402).</p><p num="0372"> A useful sta112 antigen can elicit an antibody that recognizes SEQ ID NO: 182 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 182 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 182 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta112 proteins contain variants of SEQ ID NO: 182. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 182. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 182 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 182. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 182 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0373"> The Sta112 antigen can be usefully included in the composition in combination with Sta073 [74].</p><p num="0374"> (sta113) The "sta113" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta113 is SAOUHSC_00728 and has the amino acid sequence of SEQ ID NO: 183 (GI: 88194493).</p><p num="0375"> A useful sta113 antigen can elicit an antibody that recognizes SEQ ID NO: 183 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 183 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 183 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta113 proteins contain variants of SEQ ID NO: 183. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 183. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 183 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 183. It holds one epitope. The N-terminal amino acid of the first 173 of SEQ ID NO: 183 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0376"> (sta114) The "sta114" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta114 is SAOUHSC_00810 and has the amino acid sequence of SEQ ID NO: 184 (GI: 88194570).</p><p num="0377"> A useful sta114 antigen can elicit an antibody that recognizes SEQ ID NO: 184 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 184 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 184 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta114 proteins include variants of SEQ ID NO: 184. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 184. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 184 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 184. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0378"> (sta115) The "sta115" antigen is annotated as a "virtual protein". In the NCTC8325 strain, sta115 is SAOUHSC_00817 and has the amino acid sequence of SEQ ID NO: 185 (GI: 88194576).</p><p num="0379"> A useful sta115 antigen can elicit an antibody that recognizes SEQ ID NO: 185 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 185 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 185 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta115 proteins include variants of SEQ ID NO: 185. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 185. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 185 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 185. It holds one epitope. The first 18 N-terminal amino acids of SEQ ID NO: 185 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0380"> (sta116) The "sta116" antigen has been annotated as a "formylpeptide receptor-like 1 inhibitor protein". In the NCTC8325 strain, sta116 is SAOUHSC_01112 and has the amino acid sequence of SEQ ID NO: 186 (GI: 88194858).</p><p num="0381"> A useful sta116 antigen can elicit an antibody that recognizes SEQ ID NO: 186 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 186 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 186 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta116 proteins contain variants of SEQ ID NO: 186. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 186. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 186 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 186. It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 186 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0382"> (sta117) The "sta117" antigen has been annotated as a "cut beta hemolysin". In the NCTC8325 strain, sta117 is SAOUHSC_02240 and has the amino acid sequence of SEQ ID NO: 187 (GI: 88195913).</p><p num="0383"> A useful sta117 antigen can elicit an antibody that recognizes SEQ ID NO: 187 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 187 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 187 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta117 proteins include variants of SEQ ID NO: 187. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 187. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 187 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 187. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0384"> (sta118) The "sta118" antigen is annotated as the "cell division protein FtsZ". In the NCTC8325 strain, sta118 is SAOUHSC_01150 and has the amino acid sequence of SEQ ID NO: 188 (GI: 88194892).</p><p num="0385"> A useful sta118 antigen can elicit an antibody that recognizes SEQ ID NO: 188 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 188 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 188 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These sta118 proteins include variants of SEQ ID NO: 188. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 188. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 188 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 188. It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0386"> (sta119) The "sta119" antigen is annotated as "thioredoxin". In the NCTC8325 strain, sta119 is SAOUHSC_01100 and has the amino acid sequence of SEQ ID NO: 200 (GI: 88194846).</p><p num="0387"> A useful sta119 antigen can elicit an antibody that recognizes SEQ ID NO: 200 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 200 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 200 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These sta119 proteins contain variants of SEQ ID NO: 200. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 200. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 200 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 200 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0388"> (sta120) The "sta120" antigen is annotated as "alkyl hydroperoxide reductase subunit C". In the NCTC8325 strain, sta120 is SAOUHSC_00365 and has the amino acid sequence of SEQ ID NO: 201 (GI: 88194163).</p><p num="0389"> A useful sta120 antigen can elicit an antibody that recognizes SEQ ID NO: 201 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 201 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 201 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These sta120 proteins include variants of SEQ ID NO: 201. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 201. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 201 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 201 It holds one epitope. Other fragments have one or more protein domains removed.</p><p num="0390"> (NW_6) The "NW_6" antigen has been annotated as "secretory von Bill Brandt factor binding protein precursor". In the Newman strain, NW_6 is NWMN_0757 and has the amino acid sequence of SEQ ID NO: 142 (GI: 151220969).</p><p num="0391"> A useful NW_6 antigen can elicit an antibody that recognizes SEQ ID NO: 142 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 142 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 142 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These NW_6 proteins contain variants of SEQ ID NO: 142. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 142. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 142 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 142. It holds one epitope. The first 13 N-terminal amino acids of SEQ ID NO: 142 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0392"> (NW_9) The "NW_9" antigen is annotated as a "lipoprotein". In the Newman strain, NW_9 is NWMN_0958 and has the amino acid sequence of SEQ ID NO: 143 (GI: 151221170).</p><p num="0393"> A useful NW_9 antigen can elicit an antibody that recognizes SEQ ID NO: 143 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 143 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 143 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200 or more)). These NW_9 proteins contain variants of SEQ ID NO: 143. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 143. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 143 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 143. It holds one epitope. The first 19 N-terminal amino acids of SEQ ID NO: 143 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0394"> (NW_10) The "NW_10" antigen has been annotated as a "fibrinogen binding-related protein". In the Newman strain, NW_10 is NWMN_1066 and has the amino acid sequence of SEQ ID NO: 144 (GI: 151221278).</p><p num="0395"> A useful NW_10 antigen can elicit an antibody that recognizes SEQ ID NO: 144 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 144 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 144 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These NW_10 proteins contain variants of SEQ ID NO: 144. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 144. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 144 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least of SEQ ID NO: 144 It holds one epitope. The first 20 N-terminal amino acids of SEQ ID NO: 144 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0396"> (NW_7) The "NW_7" antigen has been annotated as "staphylococcal complement inhibitor SCIN". In the Newman strain, NW_7 is NWMN_1876 and has the amino acid sequence of SEQ ID NO: 145 (GI: 151222088).</p><p num="0397"> A useful NW_7 antigen can elicit an antibody that recognizes SEQ ID NO: 145 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 145 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 145 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These NW_7 proteins contain variants of SEQ ID NO: 145. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 145. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 145 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 145. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 145 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0398"> (NW_8) The "NW_8" antigen has been annotated as "chemotaxis-inhibiting protein CHIPS". In the Newman strain, NW_8 is NWMN_1877 and has the amino acid sequence of SEQ ID NO: 146 (GI: 151222089).</p><p num="0399"> A useful NW_8 antigen can elicit an antibody that recognizes SEQ ID NO: 146 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 146 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 146 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100 or more)). These NW_8 proteins contain variants of SEQ ID NO: 146. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 146. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 146 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 146. It holds one epitope. The first 19 N-terminal amino acids of SEQ ID NO: 146 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0400"> (NW_2) The "NW_2" antigen has been annotated as an "enterotoxin type A precursor". In the Newman strain, NW_2 is NWMN_1883 and has the amino acid sequence of SEQ ID NO: 147 (GI: 151222095).</p><p num="0401"> A useful NW_2 antigen can elicit an antibody that recognizes SEQ ID NO: 147 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 147 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 147 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These NW_2 proteins contain variants of SEQ ID NO: 147. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 147. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 147 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 147. It holds one epitope. The first 16 N-terminal amino acids of SEQ ID NO: 147 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0402"> (NW_1) The "NW_1" antigen is annotated as a "lipoprotein". In the Newman strain, NW_1 is NWMN_1924 and has the amino acid sequence of SEQ ID NO: 148 (GI: 151222136).</p><p num="0403"> A useful NW_1 antigen can elicit an antibody that recognizes SEQ ID NO: 148 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 148 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 148 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150 or more)). These NW_1 proteins contain variants of SEQ ID NO: 148. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 148. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 148 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 148. It holds one epitope. The first 17 N-terminal amino acids of SEQ ID NO: 148 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0404"> (NW_5) The "NW_5" antigen is annotated as a "cell wall surface anchor family protein". In the Newman strain, NW_5 is NWMN_2392 and has the amino acid sequence of SEQ ID NO: 149 (GI: 151222604).</p><p num="0405"> A useful NW_5 antigen can elicit an antibody that recognizes SEQ ID NO: 149 (eg, when administered to humans) and / or (a) 50% or more identity with SEQ ID NO: 149 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5% or more) And / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 149 (where "n" is 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35). , 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more)). These NW_5 proteins contain variants of SEQ ID NO: 149. The preferred fragment of (b) comprises the epitope from SEQ ID NO: 149. Other preferred fragments are one or more amino acids from the C-terminus of SEQ ID NO: 149 (eg 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / or One or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) are deleted from the N-terminus, but at least in SEQ ID NO: 149. It holds one epitope. The first 52 N-terminal amino acids of SEQ ID NO: 149 can be conveniently removed. Other fragments have one or more protein domains removed.</p><p num="0406"> (Hybrid polypeptide) The antigen used in the present invention may be present in the composition as a separate polypeptide. If more than one antigen is used, however, these do not have to be isolated polypeptides. Alternatively, at least two (eg, 2, 3, 4, 5 and above) antigens can be expressed as a single polypeptide chain (hybrid polypeptide). Hybrid polypeptides offer two main advantages. First, polypeptides that may be unstable or poorly expressed on their own can be assisted by the addition of appropriate hybrid partners to overcome this problem. Second, commercial production is simplified to require the use of only one expression and purification to produce two polypeptides that are both antigenically useful.</p><p num="0407"> The hybrid polypeptide may contain two or more polypeptide sequences from the first antigen group. The hybrid polypeptide may include one or more polypeptide sequences from the first antigen group and one or more polypeptide sequences from the second antigen group. In addition, the hybrid polypeptide may contain two or more polypeptide sequences from each of the antigens listed above, or two or more variants of the same antigen if the sequences are partially variable between strains.</p><p num="0408"> Hybrids consisting of amino acid sequences from 2, 3, 4, 5, 6, 7, 8, 9 or 10 antigens are useful. In particular, hybrids consisting of amino acid sequences from 2, 3, 4 or 5 antigens, such as 2 or 3 antigens, are preferred.</p><p num="0409"> Different hybrid polypeptides may be mixed together in a single formulation. The hybrid may be combined with a non-hybrid antigen selected from the first, second or third antigen group. Of such combinations, the antigen may be present in more than one hybrid polypeptide and / or as a non-hybrid polypeptide. However, it is preferred that the antigen is present as either hybrid or non-hybrid and not both.</p><p num="0410"> The hybrid polypeptide can also be combined with a conjugate or non-S. aureus antigen as described above.</p><p num="0411"> The hybrid polypeptide is of formula NH₂-A-{-X-L-}_n-B-COOH (In the formula, X is the amino acid sequence of the S. aureus antigen, L is the optional linker amino acid sequence, and A is the optional N-terminal amino acid sequence, as discussed above. , B is an optional C-terminal amino acid sequence, and n can be represented by an integer greater than or equal to 2 (eg, 2, 3, 4, 5, 6, etc.). Usually n is 2 or 3.</p><p num="0412"> If the -X- portion has a leader peptide sequence in its wild-type form, it may be included in or omitted from the hybrid protein. In some embodiments, the leader peptide is deleted except for the -X- portion at the N-terminus of the hybrid protein, i.e., X.₁Leader peptide is retained, but X₂...X_nLeader peptide is omitted. This removes all leader peptides and X₁Is equivalent to using the leader peptide of.</p><p num="0413"> For each n case of {-XL-}, the linker amino acid sequence -L- may or may not be present. For example, if n = 2, the hybrid is NH₂-X₁-L₁-X₂-L₂-COOHNH₂-X₁-X₂-COOHNH₂-X₁-L₁-X₂-COOHNH₂-X₁-X₂-L₂-Can be COOH or the like. The linker amino acid sequence (s) -L- are typically short (eg, 20 or less amino acids, ie 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8). , 7, 6, 5, 4, 3, 2, 1). An example is a short peptide sequence that facilitates cloning, a polyglycine linker (ie Gly)._n(Including n = 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) and histidine tags (ie His)_n(N = 3, 4, 5, 6, 7, 8, 9, 10 or more)) is included. Other suitable linker amino acid sequences will be apparent to those of skill in the art. Useful linkers are GSGGGG (SEQ ID NO: 171) or GSGSGGGG (SEQ ID NO: 172) from the BamHI restriction site (or two BamHI restriction sites for the Gly-Ser dipeptide to form the tetrapeptide of SEQ ID NO: 230). As it is formed, it aids in cloning and manipulation, (Gly)₄Tetrapeptide (SEQ ID NO: 227) is a typical polyglycine linker. Especially the last L_nOther suitable linkers for use as are ASGGGS (eg, SEQ ID NO: 173 encoded by SEQ ID NO: 174) or Leu-Glu dipeptide.</p><p num="0414"> -A- is an optional N-terminal amino acid sequence. This is typically short (eg, 40 or less amino acids, ie 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). For example, a leader sequence that drives protein transport, or a short peptide sequence that facilitates cloning or purification (eg, a histidine tag, ie His)._n(N = 3, 4, 5, 6, 7, 8, 9, 10 or more)) is included. Other suitable N-terminal amino acid sequences will be apparent to those of skill in the art. X₁-A- is an N-terminal methionine, eg, Met-Ala-Ser, or an oligopeptide that provides a single Met residue (eg, 1, 2, 3) if it lacks its own N-terminal methionine. , 4, 5, 6, 7 or 8 amino acids).</p><p num="0415"> -B- is an optional C-terminal amino acid sequence. This is typically short (eg, 40 or less amino acids, ie 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1). Examples include sequences that drive protein transport, short peptide sequences that facilitate cloning or purification (eg, histidine tags, ie Hiss)._n(N = 3, 4, 5, 6, 7, 8, 9, 10 or more), eg, SEQ ID NO: 226), or sequences that enhance protein stability. Other suitable C-terminal amino acid sequences will be apparent to those of skill in the art.</p><p num="0416"> A hybrid polypeptide of the present invention may contain both EsxA and EsxB antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NOs: 151 (EsxAB; encoded by SEQ ID NO: 169) and 152 (EsxBA) are examples of such hybrids, both of which have the hexapeptide linker ASGGGS (SEQ ID NO: 173). Another "EsxAB" hybrid comprises SEQ ID NO: 241 which can be provided with N-terminal methionine (eg, SEQ ID NO: 250).</p><p num="0417"> Another hybrid polypeptide of the invention may include both SdrD and SdrE antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 168 (SdrED) is an example of such a hybrid with the hexapeptide linker ASGGGS (SEQ ID NO: 173).</p><p num="0418"> Another hybrid polypeptide of the invention may include both ClfB and SdrD antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 202 (ClfB-SdrD) is an example of such a hybrid with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 203 (SdrD-ClfB) is another example of such a hybrid with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 211 (ClfB-N3-sdrD-N3) is another example of such a hybrid in which the N3 fragment of ClfB and the N3 fragment of SdrD are joined by the hexapeptide linker ASGGGS (SEQ ID NO: 173). ..</p><p num="0419"> Another hybrid polypeptide of the invention may include both IsdA and EsxA antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 204 (IsdA-EsxA) is an example of such a hybrid with the hexapeptide linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 209 ("isdA40-184-esxA") is IsdA_40-184Is another example of such a hybrid in which is attached to EsxA via the linker ASGGGS (SEQ ID NO: 173).</p><p num="0420"> Another hybrid polypeptide of the invention may include both IsdA and sta006 antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 221 ("isdA40-184-sta006") is IsdA_40-184Is an example of such a hybrid in which is conjugated to Sta006 via the hexapeptide linker ASGGGS (SEQ ID NO: 173).</p><p num="0421"> Another hybrid polypeptide of the invention may include both Hla and sta006 antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 222 (Hla H35L-sta006) is an example of such a hybrid in which the H35L variant of Hla is conjugated to Sta006 via the hexapeptide linker ASGGGS (SEQ ID NO: 173).</p><p num="0422"> Another hybrid polypeptide of the invention may include both Hla and Emp antigens. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 205 (Hla H35L-Emp) is an example of such a hybrid in which the H35L mutant Hla is conjugated to Emp via the linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 206 (Hla27-76-Emp) is another example of such a hybrid in which the Hla fragment is attached to the Emp via the linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 207 is the H35L variant of SEQ ID NO: 206. SEQ ID NO: 208 (HlaPSGS-Emp) is another example of such a hybrid in which the Hla variant is conjugated to Emp via the linker ASGGGS (SEQ ID NO: 173).</p><p num="0423"> Another hybrid polypeptide of the invention may include IsdA antigen, EsxA antigen and EsxB antigen. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 210 ("isdA40-184-esxAB") is IsdA_40-184Is an example of such a triple hybrid conjugated to EsxAB via linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 210 contains two of these linkers, as EsxAB already contains the same linker. SEQ ID NO: 212 (IsdA-esxAB) is another example of such a triple hybrid in which IsdA is conjugated to EsxAB via the linker ASGGGS (SEQ ID NO: 173).</p><p num="0424"> Another hybrid polypeptide of the invention may include Hla antigen, EsxA antigen and EsxB antigen. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 220 (HlaH35L-esxAB) is an example of such a triple hybrid in which the H35L variant of Hla is ligated to EsxAB via the linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 220 contains two of these linkers, as EsxAB already contains the same linker. Another example of a hybrid polypeptide containing an Hla antigen, an EsxA antigen, and an EsxB antigen is that the H35L variant of Hla is ligated to EsxA via the linker APTARG (SEQ ID NO: 239) to replace its N-terminus, followed by its N-terminus. SEQ ID NO: 237 (HlaH35L-esxAB as used in the examples) is conjugated to EsxB via the linker ASGGGS (SEQ ID NO: 173) and its N-terminus is replaced. This hybrid can be provided with a suitable N-terminal sequence such as SEQ ID NO: 240.</p><p num="0425"> Another hybrid polypeptide of the invention may include the sta006 antigen, the EsxA antigen and the EsxB antigen. These may be in any order from the N-terminus to the C-terminus. SEQ ID NO: 223 (sta006-esxAB) is an example of such a triple hybrid in which sta006 is attached to EsxAB via the linker ASGGGS (SEQ ID NO: 173). SEQ ID NO: 223 contains two of these linkers, as EsxAB already contains the same linker. Another example of a hybrid polypeptide containing the sta006 antigen and the EsxA antigen and the EsxB antigen is that sta006 is ligated to EsxA via the linker APTARG (SEQ ID NO: 239) to replace its N-terminus, followed by the linker ASGGGS (sequence number 239). SEQ ID NO: 238 (sta006-esxAB as used in the examples) is conjugated to EsxB via number 173) and its N-terminus is replaced. This hybrid can be provided with a suitable N-terminal sequence such as SEQ ID NO: 240.</p><p num="0426"> Usefully, these hybrid polypeptides recognize each of the wild-type staphylococcal proteins (eg, as shown in the sequence listing) in the hybrid, eg, both wild-type EsxA and wild-type EsxB. Or both wild-type SdrD and wild-type SdrE, or both wild-type SdrD and wild-type ClfB, or both wild-type IsdA and wild-type EsxA, or wild-type IsdA and wild-type sta006. Whether to recognize both wild-type Hla and wild-type sta006, or both wild-type Hla and wild-type Emp, or wild-type IsdA and wild-type EsxA and wild-type EsxB. , Or can elicit antibodies that recognize wild-type Hla and wild-type EsxA and wild-type EsxB, or wild-type sta006 and wild-type EsxA and wild-type EsxB (eg, when administered to humans).</p><p num="0427"> (Polypeptide used in the present invention) The polypeptides used in the present invention can take various forms (eg, natural, fusion, glycosylation, non-glycosylation, lipid addition, non-lipid addition, phosphorylation, non-phosphorylation, myristoylation, non-myristoylation, Monomer, multimer, particulate, modified, etc.).</p><p num="0428"> The polypeptide used in the present invention can be prepared by various means (eg, recombinant expression, purification from cell culture, chemical synthesis, etc.). Recombinantly expressed proteins are particularly preferred for hybrid polypeptides.</p><p num="0429"> The polypeptide used in the present invention is in a purified or substantially purified form, i.e., a form that is substantially free of other polypeptides (eg, free of naturally occurring polypeptides), in particular other staphylococcal polypeptides. Alternatively, it is preferably provided in a form that is substantially free of host cell polypeptides and is generally at least about 50% pure (by weight), usually at least about 90% pure, i.e. less than about 50% of the composition. , More preferably less than about 10% (eg 5%) are composed of other expressed polypeptides. Therefore, the antigen in the composition is separated from the whole organism in which the molecule is expressed.</p><p num="0430"> The polypeptide used in the present invention is preferably a staphylococcal polypeptide.</p><p num="0431"> The term "polypeptide" refers to an amino acid polymer of arbitrary length. The polymer may be linear or branched, which may include modified amino acids, which may be interrupted by non-amino acids. The term is naturally modified or modified by intervention, eg, any other manipulation or modification such as disulfide bond formation, glycosylation, lipid addition, acetylation, phosphorylation or conjugation with a labeling component. Also includes the amino acid polymers that have been produced. For example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids) and other modifications known in the art are also included. The polypeptide can occur as a single chain or an associated chain.</p><p num="0432"> The present invention provides a polypeptide comprising the sequence -PQ- or -QP- (where -P- is the amino acid sequence defined above and -Q- is not the sequence defined above). That is, the present invention provides a fusion protein. If the N-terminus of -P- is not ATG and this codon is not present at the N-terminus of the polypeptide, it is translated as a standard amino acid for that codon rather than as Met. If this codon is at the N-terminus of the polypeptide, however, it is translated as Met. Examples of the -Q-part are not limited to them, but the histidine tag (ie His)_n(Here, n = 3, 4, 5, 6, 7, 8, 9, 10 and above)), including maltose-binding protein, or glutathione-S-transferase (GST).</p><p num="0433"> The invention also provides a process for producing a polypeptide of the invention, comprising culturing a host cell transformed with the nucleic acid of the invention under conditions that induce polypeptide expression.</p><p num="0434"> Expression of the polypeptides of the invention can occur in Staphylococcus, but the invention usually uses a heterologous host for expression (recombinant expression). The heterologous host can be a prokaryote (eg, a bacterium) or a eukaryote. This may be E. coli, but other suitable hosts include Bacillus subtilis, Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Neisseria lactamica, Neisseria cinerea, Mycobacteria (eg M. tuberculosis), yeast and the like. It is useful to modify the codons to optimize expression efficiency in such hosts without affecting the encoded amino acids as compared to the wild-type S. aureus gene encoding the polypeptides of the invention.</p><p num="0435"> The present invention provides a process for producing a polypeptide of the invention, comprising synthesizing at least a portion of the polypeptide by chemical means.</p><p num="0436"> (Nucleic acid) The present invention also provides nucleic acids encoding the polypeptides of the invention and hybrid polypeptides. The present invention also provides nucleic acids comprising nucleotide sequences encoding one or more polypeptides or hybrid polypeptides of the invention.</p><p num="0437"> The present invention also provides nucleic acids containing nucleotide sequences that have sequence identity with such nucleotide sequences. Identity between sequences is preferably determined by the Smith-Waterman homology search algorithm as described above. Such nucleic acids include those that use alternative codons to encode the same amino acid.</p><p num="0438"> The present invention also provides nucleic acids that can hybridize with these nucleic acids. Hybridization reactions can be performed under different "stringency" conditions. Conditions that increase the stringency of hybridization reactions are widely known and published in the art (eg, reference 276, p. 7.52). Examples of suitable conditions (in order of increasing stringency) are incubation temperatures of 25 ° C, 37 ° C, 50 ° C, 55 ° C and 68 ° C; 10 × SSC, 6 × SSC, 1 × SSC, Buffer concentration of 0.1 x SSC (where SSC is 0.15M Their equivalents using NaCl and 15 mM citrate buffers) and other buffer systems; formamide concentrations of 0%, 25%, 50% and 75%; incubation times of 5 minutes to 24 hours; 1, 2 More than one wash step; wash incubation time of 1, 2 or 15 minutes; as well as a wash solution of 6 x SSC, 1 x SSC, 0.1 x SSC or deionized water. Hybridization methods and their optimizations are well known in the art (see, eg, References 75, 76, 276, 278, etc.).</p><p num="0439"> In some embodiments, the nucleic acids of the invention hybridize to the target under low stringency conditions. In other embodiments, it hybridizes under moderate stringency conditions. In a preferred embodiment, it hybridizes under high stringency conditions. An exemplary set of low stringency hybridization conditions is 50 ° C and 10 × SSC. An exemplary set of moderate stringency hybridization conditions is 55 ° C and 1 × SSC. An exemplary set of high stringency hybridization conditions is 68 ° C and 0.1 × SSC.</p><p num="0440"> The present invention comprises nucleic acids containing sequences complementary to these sequences (eg, for antisense or probes, or for use as primers).</p><p num="0441"> The nucleic acids of the invention are used in hybridization reactions (eg in Northern or Southern blots, or nucleic acid microarrays or "gene chips") and amplification reactions (eg in PCR, SDA, SSSR, LCR, TMA, NASBA, etc.) and other nucleic acid techniques. Can be used.</p><p num="0442"> Nucleic acids according to the invention can take various forms (eg, single-stranded, double-stranded, vector, primer, probe, labeled, etc.). The nucleic acids of the invention may be cyclic or branched, but are generally linear. Unless otherwise stated, or otherwise required, any embodiment of the invention utilizing nucleic acids is a double-stranded form and two complementary ones constituting the double-stranded form. Both with each of the chain forms can be utilized. Primers and probes, like antisense nucleic acids, are generally single strand.</p><p num="0443"> The nucleic acids of the invention are in purified or substantially purified form, i.e., substantially free of other nucleic acids (eg, free of naturally occurring nucleic acids), especially other nucleic acids of staphylococcus or host cells. It is preferably provided in a form that is substantially free of nucleic acids and is generally at least about 50% pure (by weight), usually at least about 90% pure. The nucleic acid of the present invention is preferably a staphylococcal nucleic acid.</p><p num="0444"> The nucleic acids of the invention are shorter from the genome or cDNA library, for example by digesting longer nucleic acids with nucleases (eg restriction enzymes), for example by whole or partial chemical synthesis (eg phosphoramidite synthesis of DNA). It can be prepared by many methods, such as by joining nucleic acids or nucleotides (eg, using ligases or polymerases).</p><p num="0445"> The nucleic acids of the invention may adhere to solid supports (eg beads, plates, filters, films, slides, microarray supports, resins, etc.). The nucleic acids of the invention may be labeled, for example, with a radioactive or fluorescent or biotin label. This is especially useful when nucleic acids are used in the detection method, for example when the nucleic acids are primers or probes.</p><p num="0446"> The term "nucleic acid" generally includes the meaning of a polymer form of nucleotides of any length, including deoxyribonucleotides, ribonucleotides and / or analogs thereof. It includes DNA, RNA, and DNA / RNA hybrids. It also includes DNA or RNA analogs such as those containing modified backbones (eg, peptide nucleic acids (PNAs) or phosphorothioates) or modified bases. Therefore, the present invention includes mRNA, tRNA, rRNA, ribozyme, DNA, cDNA, recombinant nucleic acid, branched nucleic acid, plasmid, vector, probe, primer and the like. If the nucleic acids of the invention are in the form of RNA, they may or may not have a 5'cap.</p><p num="0447"> The nucleic acids of the invention may be part of a vector, i.e. a part of a nucleic acid construct designed for transduction / transfection of one or more types of cells. Vectors are, for example, "cloning vectors" designed for isolation, propagation and replication of inserted nucleotides, "expression vectors" designed for expression of nucleotide sequences in host cells, recombinant viruses or It can be a "viral vector" designed to result in the production of virus-like particles or a "shuttle vector" containing the attributes of a vector of more than one type. A preferred vector is a plasmid. A "host cell" includes an individual cell or cell culture that can or has received a foreign nucleic acid. The host cell comprises the progeny of a single host cell, which is completely identical (morphologically or wholly DNA complementary) to the original parental cell due to natural, accidental or deliberate mutations and / or alterations. It doesn't have to be (in the body). Host cells include cells transfected or infected with the nucleic acids of the invention in vivo or in vitro.</p><p num="0448"> When the nucleic acid is DNA, it is recognized that the "U" in the RNA sequence replaces the "T" in the DNA. Similarly, when the nucleic acid is RNA, it has been recognized that the "T" in the DNA sequence replaces the "U" in the RNA.</p><p num="0449"> The term "complement" or "complement" when used in connection with nucleic acids refers to Watson-Crick base pairing. That is, the complement of C is G, the complement of G is C, the complement of A is T (or U), and the complement of T (or U) is A. It is also possible to complement, for example, pyrimidines (C or T) with bases such as I (purininosin).</p><p num="0450"> The nucleic acids of the invention are, for example, to produce polypeptides; as hybridization probes for the detection of nucleic acids in biological samples; to make additional copies of nucleic acids; to make ribozymes or antisense oligonucleotides; It can be used as a single-stranded DNA primer or probe; or as a triple-strand-forming oligonucleotide.</p><p num="0451"> The present invention provides a process for producing a nucleic acid of the invention, wherein the nucleic acid is synthesized partially or entirely using chemical means.</p><p num="0452"> The present invention provides a vector containing the nucleotide sequence of the present invention (eg, a cloning or expression vector) and a host cell transformed with such a vector.</p><p num="0453"> Nucleic acid amplification according to the invention may be quantitative and / or real-time.</p><p num="0454"> For some embodiments of the invention, the nucleic acid is preferably at least 7 nucleotides in length (eg, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19). , 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45, 50, 55, 60 , 65, 70, 75, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300 nucleotides or more).</p><p num="0455"> For some embodiments of the invention, the nucleic acid is preferably at most 500 nucleotides in length (eg, 450, 400, 350, 300, 250, 200, 150, 140, 130, 120, 110, 100, 90, 80, 75, 70, 65, 60, 55, 50, 45, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15 nucleotides or less).</p><p num="0456"> The primers and probes of the invention, as well as other nucleic acids used for hybridization, are preferably 10-30 nucleotides in length (eg, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 nucleotides).</p><p num="0457"> (Strains and variants) Antigens are defined as described above by reference to existing nomenclature (eg, "ClfA"), "sta" numbers or "NW_" numbers. Table 1 herein associates these three naming / numbering systems with existing SAOUHSC numbering and / or NWMN numbering. SAOUHSC numbering refers to the genome of S. aureus NCTC8325 strain (sequenced by the Oklahoma University Health Sciences Center and disclosed in GenBank as CP000253.1; GI: 87201381), and individual SAOUHSC numbers are genomic sequences. Given as a "locus_tag" entry in the "features" section of. Similarly, NWMN numbering is disclosed in GenBank as AP009351.1 (GI: 150373012) S. aureus. Referencing the genome of the Newman strain (isolated from human infection in 1952 and having a robust virulence phenotype), the individual NWMN numbers are as "locus_tag" entries in the "features" section of the genome sequence. Given. Functional annotations for each antigen are also in the database.</p><p num="0458"> Table 1 also includes the GI number for each antigen of the invention. That is, exemplary amino acid and nucleotide sequences for any of these antigens can be readily found in public sequence databases from NCTC8325 and / or Newman strains, whereas the invention is from NCTC8325 and Newman strains. Not limited to sequences. Genome sequences of several other strains of S. aureus are available, including the MRSA strains N315 and Mu50 [77], MW2, N315, COL, MRSA252, MSSA476, RF122, USA300 (very toxic). (Highly likely), including those of JH1 and JH9. Standard search and alignment techniques can be used to identify homologues of any specific sequence from the Newman or NCTC8325 strains in any of these (or other) additional genomic sequences. In addition, the sequences available from the Newman and NCTC8325 strains can be used to design primers for amplification of homologous sequences from other strains. Thus, the invention is not limited to these two strains, but rather includes such variants and homologues from other strains of S. aureus, as well as non-natural variants. In general, suitable variants of a specific SEQ ID NO: include its allelic variant, its polymorph, its homologue, its ortholog, its paralog, its variant, and the like.</p><p num="0459"> Thus, for example, the polypeptide used in the present invention may have a 1 or such as a conservative substitution (ie, substitution of one amino acid with another amino acid having a related side chain) as compared to SEQ ID NOs in the present specification. It may contain multiple amino acid substitutions (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.). Amino acids encoded by genes are generally divided into four families: (1) acidic, i.e. aspartic acid, glutamic acid; (2) basic, i.e. lysine, arginine, histidine; (3) non-polar, i.e. alanine. , Valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polarities, namely glycine, aspartin, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan and tyrosine are occasionally classified together as aromatic amino acids. In general, single amino acid substitutions within these families do not have a significant effect on biological activity. The polypeptide may also contain one or more single amino acid deletions (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, etc.) for the sequence of SEQ ID NO:. Polypeptides also include one or more insertions (eg 1, 2, 3, 4 or 5 amino acids) to the sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, etc. Each) may be included.</p><p num="0460"> Similarly, the polypeptide used in the present invention Same as the sequence disclosed in the sequence listing (ie 100% identical); Has sequence identity with the sequences disclosed in the sequence listing (eg 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99). %, 99.5% or more);1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 (or better) that can be distant or continuous compared to the sequence of (a) or (b) Has many) single amino acid changes (deletion, insertion, substitution); andWhen aligned with a specific sequence from a sequence table using a pairwise alignment algorithm, each movement window of x amino acids from the N-terminal to the C-terminal (for alignment extending to p-amino acids, if p&gt; x, The same aligned amino acids of at least xy (where x is 20, 25, 30, 35, 40, 45, 50, 60, so that such a window of p-x + 1 exists) Choose from 70, 80, 90, 100, 150, 200; y from 0.50, 0.60, 0.70, 0.75, 0.80, 0.85, 0.90, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96, 0.97, 0.98, 0.99 Selected; may contain an amino acid sequence having (round up to the nearest integer if xy is not an integer). A preferred pairwise alignment algorithm is the Needleman-Wunsch global alignment algorithm [78] with default parameters (eg, gap opening penalty = 10.0 and gap extension penalty = 0.5 using the EBLOSUM62 scoring matrix). This algorithm is conveniently implemented in the needle tool in the EMBOSS package [79].</p><p num="0461"> When using a hybrid polypeptide, the individual antigens (ie, individual -X-parts) in the hybrid may be from one or more strains. If n = 2, for example, X₂Is X₁It may be from the same strain or a different strain. If n = 3, the stock is (i) X₁=X₂=X₃, (Ii) X₁=X₂X3,(iii)X₁ X₂=X₃(Iv) X₁ X₂ X₃Or (v) X₁=X₃ X₂And so on.</p><p num="0462"> Of group (c), the deletion or substitution may be at the N-terminus and / or C-terminus, or between the two terminus. Thus, cleavage is an example of a deletion. Cleavage can include deletions of up to 40 (or more) amino acids at the N-terminus and / or C-terminus. N-terminal cleavage can remove the leader peptide and promote recombinant expression, for example in a heterologous host. C-terminal cleavage can remove anchor sequences and promote recombinant expression, for example in heterologous hosts.</p><p num="0463"> In general, if the antigen contains a sequence that is not identical to the complete S. aureus sequence from the sequence listing (eg, a sequence in which the antigen has &lt;100% sequence identity to the complete S. aureus sequence). In each individual case), it is preferred that the antigen be able to elicit an antibody that recognizes the respective complete S. aureus sequence.</p><p num="0464"> (Mutant bacteria) The present invention also provides S. aureus bacteria in which one or more of the antigens from the various antigen groups of the present invention have been knocked out. Techniques for producing knockout bacteria are well known and knockout S. aureus strains have been reported. The knockout mutation may be located in the coding region of the gene or in its transcriptional regulatory region (eg, within its promoter). Knockout mutations reduce the level of mRNA encoding the antigen to &lt;1%, preferably &lt;0.5%, more preferably &lt;0.1% and most preferably 0% of those produced by wild-type bacteria.</p><p num="0465"> The present invention also provides S. aureus in which one or more of the antigens from the various antigen groups of the present invention have mutations that inhibit their activity. The gene encoding the antigen has a mutation that alters the encoded amino acid sequence. Mutations may include deletions, substitutions and / or insertions, any of which may involve one or more amino acids.</p><p num="0466"> The present invention also provides a bacterium such as S. aureus bacterium that overexpresses the antigen of the present invention.</p><p num="0467"> The present invention also provides a bacterium such as S. aureus bacterium that constitutively expresses the antigen of the present invention. The present invention also provides Neisseria meningitidis, which comprises a gene encoding the antigen of the present invention, wherein the gene is under the control of an inducible promoter.</p><p num="0468"> (Immunogenic compositions and pharmaceuticals) The immunogenic composition of the present invention may be useful as a vaccine. Vaccines according to the invention may be either prophylactic (ie, prevent infection) or therapeutic (ie, treat infection), but are typically prophylactic.</p><p num="0469"> The composition is therefore pharmaceutically acceptable. They usually contain components in addition to the antigen, eg, they typically contain one or more pharmaceutical carriers and / or excipients. A detailed discussion of such components is available in reference 273.</p><p num="0470"> The composition is generally administered to mammals in aqueous form. However, prior to administration, the composition may be in non-aqueous form. For example, some vaccines are produced in aqueous form, then filled and delivered, and also administered in aqueous form, while other vaccines are lyophilized during production and reconstituted in aqueous form upon use. Thus, the compositions of the present invention can be dried like lyophilized formulations.</p><p num="0471"> The composition may include preservatives such as thiomersal or 2-phenoxyethanol. However, preferably, the vaccine should be substantially free of mercury substances (ie less than 5 μg / ml), eg, thiomersal. Vaccines that do not contain mercury are more preferred. Vaccines that do not contain preservatives are particularly preferred.</p><p num="0472"> To improve thermal stability, the composition may include a temperature protectant. Further details of such agents are described below.</p><p num="0473"> It is preferable to include a physiological salt such as a sodium salt in order to control the tonicity. Sodium chloride (NaCl) is preferred, which may be present at 1-20 mg / ml, for example about 10 ± 2 mg / ml NaCl. Other salts that may be present include potassium chloride, potassium dihydrogen phosphate, disodium phosphate anhydride, magnesium chloride, calcium chloride and the like.</p><p num="0474"> The composition generally has a weight osmolal concentration of 200 mOsm / kg to 400 mOsm / kg, preferably 240 to 360 mOsm / kg, more preferably in the range of 290 to 310 mOsm / kg.</p><p num="0475"> The composition may include one or more buffers. Typical buffers include phosphate buffers, Tris buffers, borate buffers, succinic acid buffers, histidine buffers (especially with aluminum hydroxide adjuvant) or citrate buffers. The buffer is typically contained in the range of 5-20 mM.</p><p num="0476"> The pH of the composition is generally 5.0 to 8.1 and more typically 6.0 to 8.0, such as 6.5 and 7.5, or 7.0 to 7.8.</p><p num="0477"> The composition is preferably sterilized. The composition is preferably pyrogen-free and contains, for example, &lt;1 EU per dose (endotoxin unit, standard scale), preferably &lt;0.1 EU per dose. The composition is preferably gluten-free.</p><p num="0478"> The composition may contain a substance for a single immunization or a substance for multiple immunizations (ie, a "multiple dose" kit). Preservatives are preferably included in the multi-dose configuration. Instead of including (or in addition to) the preservative in the multi-dose composition, the composition may be placed in a container with a sterile adapter to remove the material.</p><p num="0479"> Human vaccines are typically given in a dose volume of about 0.5 ml, but children may be given half the dose (ie about 0.25 ml).</p><p num="0480"> The immunogenic composition of the present invention may also include one or more immunomodulators. Preferably, one or more of the immunomodulators comprises one or more adjuvants. The adjuvant may include a TH1 adjuvant and / or a TH2 adjuvant discussed further below.</p><p num="0481"> Therefore, the present invention (1) With one or more antigens selected from the 1st, 2nd, 3rd and 4th antigen groups (as defined above). (2) With an adjuvant such as an aluminum hydroxide adjuvant (eg, one or more antigens may be adsorbed on aluminum hydroxide) Provided is an immunogenic composition comprising the combination of.</p><p num="0482"> For example, the present invention provides an immunogenic composition comprising a combination of a sta006 antigen and an adjuvant such as an aluminum hydroxide adjuvant. Similarly, the present invention provides an immunogenic composition comprising a combination of the sta011 antigen and an adjuvant such as an aluminum hydroxide adjuvant. These compositions are ideally buffered with, for example, histidine buffer.</p><p num="0483"> The adjuvants that can be used in the compositions of the present invention include, but are not limited to, the following.</p><p num="0484"> (A. Inorganic substance-containing composition) Inorganic-containing compositions suitable for use as adjuvants in the present invention include inorganic salts such as aluminum salts and calcium salts (or mixtures thereof). Calcium salts include calcium phosphate (eg, "CAP" particles disclosed in Reference 80). Aluminum salts include hydroxides, phosphates, sulfates, etc., and these salts take any suitable form (eg, gel, crystalline, amorphous, etc.). It is preferably adsorbed on these salts (eg, all antigens may be adsorbed). Inorganic- containing compositions may also be formulated as particles of metal salts [81].</p><p num="0485"> An adjuvant known as aluminum hydroxide and aluminum phosphate may be used. These names are common, but are used only for convenience. This is because none of these accurately describe the actual chemicals present (see, eg, Chapter 9 of Reference 82). The present invention can use either "hydroxide" or "phosphate" adjuvants, which are commonly used as adjuvants. The adjuvant known as "aluminum hydroxide" is typically an aluminum hydroxide salt, which is usually at least partially crystalline. The adjuvant known as "aluminum phosphate" is typically aluminum hydroxyphosphate, which also frequently contains small amounts of sulfate (ie, aluminum hydroxyphosphate sulfate). These can be obtained by precipitation, and the reaction conditions and concentration during precipitation affect the degree of substitution of phosphate for hydroxyl in the salt.</p><p num="0486"> For aluminum hydroxide adjuvants, fibrous forms (eg, as observed in transmission electron micrographs) are typical. The pI of an aluminum hydroxide adjuvant is typically about 11, i.e. the adjuvant itself has a positive surface charge at physiological pH. Al at pH 7.4⁺⁺⁺A protein adsorption capacity of 1.8-2.6 mg per mg has been reported for aluminum hydroxide adjuvants.</p><p num="0487"> Aluminum phosphate adjuvants generally have a PO of 0.3-1.2, preferably 0.8-1.2, more preferably 0.95 ± 0.1.₄Has a / Al molar ratio. Aluminum phosphate is generally amorphous, especially for hydroxyphosphates. A typical adjuvant is a PO of 0.84 to 0.92₄Amorphous aluminum hydroxyphosphate with a / Al molar ratio, 0.6 mg Al³⁺Included in / ml. Aluminum phosphate is generally particulate (eg, plate-like morphology as observed in transmission electron micrographs). The typical diameter of the particles is in the range of 0.5-20 μm (eg about 5-10 μm) after adsorption of any antigen. Al at pH 7.4⁺⁺⁺A protein adsorption capacity of 0.7-1.5 mg per mg has been reported for an aluminum phosphate adjuvant.</p><p num="0488"> The zero charge point (PZC) of aluminum phosphate is inversely proportional to the degree of phosphate substitution for hydroxyl, which varies depending on the reaction conditions used to prepare the salt by precipitation and the concentration of the reactants. it can. PZC can be achieved by varying the concentration of free phosphate ions in solution (more phosphate = more acidic PZC) or by adding a buffer such as a histidine buffer (making PZC more basic). Will also be changed. Aluminum phosphate used according to the present invention generally has a PZC of 4.0-7.0, more preferably 5.0-6.5, for example about 5.7.</p><p num="0489"> Adsorption of S. aureus protein antigens (except IsdA, Sta019 and Sta073) to an aluminum hydroxide adjuvant is particularly advantageous in multiple protein combinations (all antigens may be adsorbed), as shown below. .. Histidine buffers can be usefully included in such adjuvanted compositions.</p><p num="0490"> The aluminum salt suspension used to prepare the compositions of the present invention may contain a buffer (eg, phosphate buffer or histidine buffer or Tris buffer), but this is always required. Do not mean. The suspension is preferably sterile and free of pyrogens. The suspension may contain free aqueous phosphate ions present at a concentration of, for example, 1.0 to 20 mM, preferably 5 to 15 mM, more preferably about 10 mM. The suspension may also include sodium chloride.</p><p num="0491"> The present invention can use a mixture of both aluminum hydroxide and aluminum phosphate. In this case, there may be more aluminum phosphate than aluminum hydroxide, eg, at least 2: 1, eg 5: 1, 6: 1, 7: 1, 8: 1, 9: 1. It may be a weight ratio such as.</p><p num="0492"> Al in the composition for administration to the patient⁺⁺⁺The concentration of is preferably less than 10 mg / ml, for example, 5 mg / ml, 4 mg / ml, 3 mg / ml, 2 mg / ml, 1 mg / ml, and the like. The preferred range is 0.3 to 1 mg / ml. A maximum of 0.85 mg / dose is preferred.</p><p num="0493"> (B. Oily emulsion) Suitable oily emulsion compositions for use as an adjuvant in the present invention are MF59 [see also Chapter 10 of Reference 82; Reference 83] (prescribed to submicron particles using a microfluidizer 5). Includes squalene-water emulsions such as% squalene, 0.5% Tween80 and 0.5% Span85). Complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA) may also be used.</p><p num="0494"> Various oil-in-water emulsion adjuvants are known, which typically include at least one oil and at least one surfactant, the oil (s) and the surfactant (s). Is biodegradable (metabolizable) and biocompatible. The oil droplets in the emulsion are typically less than 5 μm in diameter, ideally having a submicron diameter, and these small sizes are achieved using a microfluidizer to provide a stable emulsion. Droplets with a size of less than 220 nm are preferred as they can be subjected to filter sterilization.</p><p num="0495"> Emulsions can include oils such as those from animal (eg fish) or plant sources. Sources of vegetable oils include nuts, seeds and grains. Peanut oil, soybean oil, coconut oil and olive oil are examples of the most commonly available nut oils. For example, jojoba oil obtained from jojoba beans can be used. Seed oil includes safflower oil, cottonseed oil, sunflower seed oil, sesame oil and the like. In the cereal group, corn oil is most readily available, but cereal oils from other cereals such as wheat, oats, rye, rice, teff, triticale, etc. may also be used. 6-10 carbon fatty acid esters of glycerol and 1,2-propanediol are not naturally present in seed oils, but are prepared by hydrolysis, separation and esterification of suitable materials starting from fruit oils and seed oils. obtain. Fats and oils from mammalian milk are metabolizable and may therefore be used in the practice of the present invention. Procedures for separation, purification, saponification and other means required to obtain pure oil from animal sources are well known in the art. Most fish contain metabolizable oils that can be easily collected. For example, whale oils such as cod liver oil, shark liver oil and whale wax are some examples of fish oils that can be used herein. Several branched chain oils are biochemically synthesized in 5-carbon isoprene units and are commonly referred to as terpenoids. Shark liver oil contains a branched unsaturated terpenoid known as squalene, 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene. Particularly preferred herein. Squalane, a saturated analog of squalene, is also a preferred oil. Fish oils containing squalene and squalene are readily available from commercial sources or can be obtained by methods known in the art. Another preferred oil is tocopherol (see below). A mixed oil can be used.</p><p num="0496"> Surfactants can be classified by their "HLB" (hydrophilic / lipophilic balance). Preferred surfactants of the invention have at least 10, preferably at least 15, more preferably at least 16 HLBs. The present invention is limited to, but not limited to, polyoxyethylene sorbitan ester surfactants (commonly referred to as Tween), especially DOWFAX such as polysorbate 20 and polysorbate 80; linear EO / PO block copolymers.^TMCopolymers of ethylene oxide (EO), propylene oxide (PO) and / or butylene oxide (BO) sold under the trade name of; Octoxy, in which the number of repeating ethoxy (oxy-1,2-ethanediyl) groups can vary. Nords, especially octoxinol-9 (Triton X-100 or t-octylphenoxypolyethoxyethanol), are of interest; (octylphenoxy) polyethoxyethanol (IGEPAL CA-630 / NP-40); Lipid; Tergitol^TMNonoxynols ethoxylates such as the NP series; polyoxyethylene fatty ethers (known as Brij surfactants) derived from lauryl, cetyl, stearyl and oleyl alcohols such as triethylene glycol monolauryl ether (Brij30); and sorbitan. Surfactants containing sorbitan esters (commonly known as SPAN) such as trioleate (Span85) and sorbitan monolaurate can be used. Nonionic surfactants are preferred. Preferred surfactants to include in the emulsion are Tween80 (polyoxyethylene sorbitan monooleate), Span85 (sorbitan trioleate), lecithin and Triton X-100.</p><p num="0497"> A mixture of surfactants, such as a Tween80 / Span85 mixture, can be used. Combinations of polyoxyethylene sorbitan esters such as polyoxyethylene sorbitan monooleate (Tween 80) with octoxinol such as t-octylphenoxypolyethoxyethanol (Triton X-100) are also suitable. Another useful combination includes laureth-9 and polyoxyethylene sorbitan ester and / or octoxinol.</p><p num="0498"> The preferred amount (% by weight) of surfactant is polyoxyethylene sorbitan ester (eg Tween80) 0.01-1%, especially about 0.1%; octyl- or nonylphenoxypolyoxyethanol (eg Triton X-100 or other in the Triton series). Detergent) 0.001 to 0.1%, especially 0.005 to 0.02%; polyoxyethylene ether (eg, laureth 9) 0.1 to 20%, preferably 0.1 to 10%, especially 0.1 to 1% or about 0.5%.</p><p num="0499"> Preferred emulsion adjuvants have an average droplet size of &lt;1 μm, such as 750 nm, 500 nm, 400 nm, 300 nm, 250 nm, 220 nm, 200 nm or less. These droplet sizes can be easily achieved by techniques such as microfluidization.</p><p num="0500"> Specific oil-in-water emulsion adjuvants useful in the present invention include, but are not limited to,:</p><p num="0501"> -Squalene, Tween80 and Span85 submicron emulsions. The composition by volume of the emulsion can be about 5% squalene, about 0.5% polysorbate 80 and about 0.5% Span85. In terms of weight, these ratios are 4.3% squalene, 0.5% polysorbate 80 and 0.48% Span85. This adjuvant is known as "MF59" [84-86], as described in more detail in Chapter 10 of Reference 87 and Chapter 12 of Reference 88. Advantageously, the MF59 emulsion contains citrate ions, such as 10 mM sodium citrate buffer.</p><p num="0502"> -Emulsion of squalene, tocopherol and polysorbate 80 (Tween 80). The emulsion may include phosphate buffered saline. It may also include Span85 (eg at 1%) and / or lecithin. These emulsions may have 2-10% squalene, 2-10% tocopherols and 0.3-3% Tween80, with a weight ratio of squalene: tocopherols preferably 1 as a more stable emulsion is obtained. is there. Squalene and Tween 80 may be present in a volume ratio of about 5: 2 or a weight ratio of about 11: 5. Some such emulsions dissolve Tween80 in PBS to give a 2% solution, then mix 90 ml of this solution with a mixture of (5 g DL-α-tocopherol and 5 ml squalene), then mix the mixture. It can be produced by microfluidizing. The resulting emulsion may have submicron oil droplets with an average diameter of, for example, 100-250 nm, preferably about 180 nm. The emulsion may also contain 3-de-O-acetylated monophosphoryl lipid A (3d-MPL). Another useful emulsion of this type may contain 0.5-10 mg squalene, 0.5-11 mg tocopherol and 0.1-4 mg polysorbate 80 per human dose [89].</p><p num="0503"> -Emulsions of squalene, tocopherols and Triton cleaners (eg Triton X-100). The emulsion may also contain 3d-MPL (see below). The emulsion may contain a phosphate buffer.</p><p num="0504"> -Emulsion containing polysorbate (eg, polysorbate 80), Triton detergent (eg, Triton X-100) and tocopherol (eg, tocopherol α-succinate). The emulsion may contain these three components in a mass ratio of about 75:11:10 (eg, 750 μg / ml polysorbate 80, 110 μg / ml Triton X-100 and 100 μg / ml α-tocopherol succinate) and their concentrations. Should include the contribution of any of these components from the antigen. The emulsion may also contain squalene. The emulsion may also contain 3d-MPL (see below). The aqueous phase may contain a phosphate buffer.</p><p num="0505"> Squalane, Polysorbate 80 and Poloxamer 401 ("Pluronic"^TML121 ") emulsion. The emulsion can be formulated in phosphate buffered saline, pH 7.4. This emulsion is a useful delivery vehicle for muramyl dipeptide and is used in the "SAF-1" adjuvant along with threonyl-MDP [90] (0.05-1% Thr-MDP, 5% squalane, 2.5%). Pluronic L121 and 0.2% polysorbate 80). It can also be used without Thr-MDP, as with the "AF" adjuvant [91] (5% squalane, 1.25% Pluronic L121 and 0.2% polysorbate 80). Microfluidization is preferred.</p><p num="0506"> Squalene, aqueous solvents, polyoxyethylene alkyl ethers such as hydrophilic nonionic surfactants (eg polyoxyethylene (12) cetostearyl ethers) and hydrophobic nonionic surfactants (eg sorbitan monooleate or "Span 80"). Emulsion containing sorbitan ester or mannide ester). Emulsions are preferably thermoreversible and / or at least 90% oil droplets (depending on volume) in size less than 200 nm [92]. The emulsion may also contain one or more of alditol, cryoprotectants (eg, sugars such as dodecyl maltoside and / or sucrose), and / or alkyl polyglycosides. The emulsion may include a TLR4 agonist [93]. Such emulsions may be lyophilized.</p><p num="0507"> -Emulsion of squalene, poloxamer 105 and Abil-Care [94]. The final concentration (weight) of these components in the adjuvanted vaccine is 5% squalene, 4% poloxamer 105 (pluronic polyol) and 2% Abil-Care85 (bis-PEG / PPG-16 / 16 PEG / PPG-16). / 16 dimethicone; caprylic acid / capric acid triglyceride).</p><p num="0508"> An emulsion containing .0.5-50% oil, 0.1-10% phospholipids and 0.05-5% nonionic surfactant. As described in Reference 95, preferred phospholipid components are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, phosphatidic acid, sphingomyelin and cardiolipin. Submicron droplet size is advantageous.</p><p num="0509"> -Submicron oil-in-water emulsions of non-metabolizable oils (eg light oil) and at least one surfactant (eg lecithin, Tween 80 or Span 80). QuilA saponin, cholesterol, saponin lipophilic conjugate (eg, GPI-0100 described in Reference 96, produced by adding an aliphatic amine to desacyl saponin via the carboxyl group of glucuronic acid), dimethyl Dimethyidioctadecylammonium bromide and / or additives such as N, N-dioctadecylammonium-N, N-bis (2-hydroxyethyl) propanediamine may be included.</p><p num="0510"> An emulsion in which saponins (eg QuilA or QS21) and sterols (eg cholesterol) are associated as helical micelles [97].</p><p num="0511"> Emulsions containing mineral oils, nonionic lipophilic ethoxylated fatty alcohols and nonionic hydrophilic surfactants (eg, ethoxylated fatty alcohols and / or polyoxyethylene-polyoxypropylene block copolymers) [98].</p><p num="0512"> Emulsions containing mineral oils, nonionic hydrophilic ethoxylated fatty alcohols and nonionic lipophilic surfactants (eg, ethoxylated fatty alcohols and / or polyoxyethylene-polyoxypropylene block copolymers) [98].</p><p num="0513"> In some embodiments, the emulsion may be instantly mixed with the antigen upon delivery, thus the adjuvant and antigen are separate in the packaged or dispensed vaccine prepared for the final formulation at the time of use. Can be stored in. In other embodiments, the emulsion is mixed with the antigen during production and thus the composition is packaged in a liquid adjuvant-added form. The antigen is generally in an aqueous form such that the vaccine is finally prepared by mixing the two liquids. The volume ratio of the two liquids for mixing can vary (eg 5: 1 to 1: 5), but is generally about 1: 1. Where the concentrations of the ingredients are indicated in the above description of the specific emulsion, these concentrations are typically for an undiluted composition and the concentration after mixing with the antigen solution is Therefore, it decreases.</p><p num="0514"> When the composition contains tocopherols, any of α, β, γ, δ, ε or ξ tocopherols can be used, but α-tocopherols are preferred. Tocopherols can take several forms, such as different salts and / or isomers. Salts include organic salts such as succinate, acetate, nicotinate and the like. Both D-α-tocopherol and DL-α-tocopherol can be used. Tocopherol is advantageously included in vaccines for elderly patients (eg, age 60+). This is because vitamin E has been reported to have a positive effect on the immune response in this group of patients [99]. They also have antioxidant properties that can help stabilize the emulsion [100]. The preferred α-tocopherol is DL-α-tocopherol, and the preferred salt of this tocopherol is succinate. Succinates have been found to work with TNF-related ligands in vivo.</p><p num="0515"> (C. Saponin Prescription [Chapter 22 of Reference 82]) The saponin formulation may be used as an adjuvant in the present invention. Saponins are a heterogeneous group of sterol glycosides and triterpenoid glycosides found in the bark, leaves, stems, roots and even flowers of a wide variety of plants. Saponins from the bark of the Quillaia saponaria Molina tree have been widely studied as an adjuvant. Saponins can also be obtained commercially from Smilax ornata (sarsaprilla), Gypsophilla paniculata (blythe veil) and Saponaria officianalis (soap root). Saponin adjuvant formulations include purified formulations such as QS21 and lipid formulations such as ISCOM. QS21 is Stimulon^TMIt is commercially available as.</p><p num="0516"> The saponin composition has been purified using HPLC and RP-HPLC. Specific purified fractions using these techniques have been identified, including QS7, QS17, QS18, QS21, QH-A, QH-B and QH-C. Preferably, the saponin is QS21. A method for producing QS21 is disclosed in reference 101. Saponin formulations may also include sterols such as cholesterol [102].</p><p num="0517"> The combination of saponin and cholesterol can be used to form unique particles called immunostimulatory complexes (ISCOM) [Reference 82, Chapter 23]. ISCOM also typically also contains phospholipids such as phosphatidylethanolamine or phosphatidylcholine. Any known saponin can be used in ISCOM. Preferably, ISCOM comprises one or more of QuilA, QHA and QHC. ISCOM is further described in references 102-104. If desired, ISCOMS may lack additional cleaning agents [105].</p><p num="0518"> An overview of the development of saponin-based adjuvants can be found in references 106 and 107.</p><p num="0519"> (D. Birosome and virus-like particles) Virosomes and virus-like particles (VLPs) can also be used as adjuvants in the present invention. These structures generally contain one or more proteins from the virus that are optionally combined with or formulated with phospholipids. They are generally non-pathogenic, non-replicating and generally do not contain any native viral genome. Viral proteins may be recombinantly produced or isolated from the entire virus. Suitable viral proteins for use in bacteriophages or VLPs include influenza virus (eg HA or NA), hepatitis B virus (eg core or capsid protein), hepatitis E virus, measles virus, sinobis virus, rotavirus. , Mouth epidemic virus, retrovirus, nowalk virus, human papillomavirus, HIV, RNA phage, Qβ phage (eg coat protein), GA phage, fr phage, AP205 phage and Ty (eg retrotransposon Ty protein p1) derived proteins Including. VLPs are further discussed in references 108-113. Birosomes are further discussed, for example, in reference 114.</p><p num="0520"> (E. Bacterial or microbial derivative) Suitable adjuvants for use in the present invention are non-toxic derivatives of Gut microbiota lipopolysaccharide (LPS), lipid A derivatives, immunostimulatory oligonucleotides and bacterial or microbial derivatives such as ADP-ribosylated toxin and its detoxified derivatives. including.</p><p num="0521"> Non-toxic derivatives of LPS include monophosphoryl lipid A (MPL) and 3-O-deacylated MPL (3dMPL). 3dMPL is a mixture of 3-de-O-acylated monophosphoryl lipid A with 4, 5 or 6 acylated chains. The preferred "small particle" form of 3-de-O-acylated monophosphoryl lipid A is disclosed in reference 115. Such "small particles" of 3dMPL are small enough to be sterile filtered through a 0.22 μm membrane [115]. Other non-toxic LPS derivatives include aminoalkyl glucosaminide phosphate derivatives, such as monophosphoryl lipid A mimetics such as RC-529 [116, 117].</p><p num="0522"> Lipid A derivatives include derivatives of Lipid A from Escherichia coli such as OM-174. OM-174 is described, for example, in references 118 and 119.</p><p num="0523"> Immunostimulatory oligonucleotides suitable for use as adjuvants in the present invention include nucleotide sequences containing the CpG motif, a dinucleotide sequence containing unmethylated cytosine linked to guanosine by phosphate binding. Oligonucleotides containing double-stranded RNA and palindromic or poly (dG) sequences have also been shown to be immunostimulatory.</p><p num="0524"> CpG can include nucleotide modifications / analogs such as phosphorothioate modifications and can be double-stranded or single-stranded. References 120, 121 and 122 disclose possible analog substitutions, such as guanosine replacement with 2'-deoxy-7-deazaguanosine. The adjuvant effect of CpG oligonucleotides is further discussed in references 123-128.</p><p num="0525"> The CpG sequence may be directed to TLR9, such as the motif GTCGTT or TTCGTT [129]. The CpG sequence can be specific for inducing a Th1 immune response, such as CpG-A ODN, or more specific for inducing a B cell response, such as CpG-B ODN. CpG-A and CpG-B ODN are discussed in references 130-132. Preferably, the CpG is CpG-A ODN.</p><p num="0526"> Preferably, the CpG oligonucleotide is constructed so that the 5'end can be approached for receptor recognition. If desired, the two CpG oligonucleotide sequences may be attached at their 3'ends to form an "immunomer". See, for example, references 129 and 133-135.</p><p num="0527"> A useful CpG adjuvant is ProMune^TM(Coley Pharmaceutical Group, Inc.) is also known as CpG7909. Another is CpG1826. Instead of or in addition to using CpG sequences, TpG sequences can be used [136] and these oligonucleotides may not contain unmethylated CpG motifs. The immunostimulatory oligonucleotide may be pyrimidine-rich. For example, it may contain more than 1 contiguous thymidine nucleotide (eg, TTTT as disclosed in Reference 136) and / or it may contain&gt; 25% thymidine (eg&gt; 35%,&gt; 40%,&gt;. It may have a nucleotide composition having (50%,&gt; 60%,&gt; 80%, etc.). For example, it may contain more than 1 contiguous cytosine nucleotide (eg CCCC as disclosed in Reference 136) and / or this may contain&gt; 25% cytosine (eg&gt; 35%,&gt; 40%,&gt;. It may have a nucleotide composition having (50%,&gt; 60%,&gt; 80%, etc.). These oligonucleotides may not contain unmethylated CpG motifs. Immunostimulatory oligonucleotides typically contain at least 20 nucleotides. These may contain less than 100 nucleotides.</p><p num="0528"> A particularly useful adjuvant based on immunostimulatory oligonucleotides is IC-31.^TMKnown as [137]. Thus, the adjuvants used in the present invention are (i) oligonucleotides (eg, 15-40 nucleotides) containing at least one (preferably multiple) CpI motifs (ie, cytosines linked to inosin to form dinucleotides). ) And (ii) a mixture of polycationic polymers such as oligopeptides (eg, 5-20 amino acids) containing at least one (preferably multiple) Lys-Arg-Lys tripeptide sequences. The oligonucleotide has a 26-mer sequence 5'-(IC).₁₃It may be a deoxynucleotide containing -3'(SEQ ID NO: 175). The polycationic polymer may be a peptide comprising the 11-mer amino acid sequence KLKLLLLLKLK (SEQ ID NO: 176). Oligonucleotides and polymers can form complexes, for example as disclosed in references 138 and 139.</p><p num="0529"> Bacterial ADP ribosylation toxin and its detoxifying derivatives may be used as an adjuvant in the present invention. Preferably, the protein is derived from E. coli (E. coli heat-labile enterotoxin "LT"), cholera ("CT") or whooping cough ("PT"). The use of detoxified ADP ribosylated toxin as a mucosal adjuvant is described in Reference 140 and its use as a parenteral adjuvant is described in Reference 141. The toxin or toxoid is preferably in the form of a holotoxin containing both subunits A and B. Preferably, the A subunit contains a detoxification mutation, and preferably the B subunit is unmutated. Preferably, the adjuvant is a detoxified LT mutant such as LT-K63, LT-R72 and LT-G192. The use of ADP ribosylation toxin and its detoxifying derivatives as adjuvants, especially LT-K63 and LT-R72, can be found in references 142-149. A useful CT variant is CT-E29H [150]. Numerical references for amino acid substitutions are preferably based on the alignment of the A and B subunits of the ADP ribosylation toxin set forth in reference 151, which is incorporated herein by reference in its entirety. ..</p><p num="0530"> (F.Human immunomodulatory substance) Suitable human immunomodulators for use as adjuvants in the present invention are interleukins (eg IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12 [152]. Etc.) [153], including cytokines such as interferon (eg, interferon-γ), macrophage colony stimulating factor, and tumor necrosis factor. A preferred immunomodulator is IL-12.</p><p num="0531"> (G. Bioadhesive and mucoadhesive) Bioadhesive substances and mucosal adherent substances may also be used as adjuvants in the present invention. Suitable bioadhesive materials include esterified hyaluronic acid microspheres [154], or mucoadhesive materials such as poly (acrylic acid), polyvinyl alcohol, polyvinylpyrrolidone, polysaccharides and crosslinked derivatives of carboxymethyl cellulose. Chitosan and its derivatives may also be used as an adjuvant in the present invention [155].</p><p num="0532"> (H. Tiny particles) Fine particles may also be used as an adjuvant in the present invention. Formed in addition to poly (lactide-co-glycolide), biodegradable and non-toxic substances (eg poly (α-hydroxy acids), polyhydroxybutyrate, polyorthoesters, polyanhydrides, polycaprolactone, etc.) Fine particles (ie, particles with a diameter of about 100 nm to about 150 μm, more preferably particles with a diameter of about 200 nm to about 30 μm, most preferably particles with a diameter of about 500 nm to about 10 μm) are preferred, and these are optionally negatively charged surfaces (eg, for example). Treated to have a surface (with SDS) or a positively charged surface (eg with a cationic cleaning agent such as CTAB).</p><p num="0533"> (I. Liposomes (Chapter 13 and 14 of Reference 82)) Examples of liposome formulations suitable for use as an adjuvant are described in references 156-158.</p><p num="0534"> (J. Polyoxyethylene ether and polyoxyethylene ester formulations) Suitable adjuvants for use in the present invention include polyoxyethylene ethers and polyoxyethylene esters [159]. Such formulations are further combined with a polyoxyethylene sorbitan ester surfactant [160] in combination with octoxinol, and polyoxyethylene in combination with at least one additional nonionic surfactant such as octoxinol. Contains alkyl ether or ester surfactants [161]. Preferred polyoxyethylene ethers are selected from the following groups: polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-steoryl ether, polyoxytheylene-8-stearyl. Ether, polyoxyethylene-4-lauryl ether, polyoxyethylene-35-lauryl ether, and polyoxyethylene-23-lauryl ether.</p><p num="0535"> (K. Phosphazene) For example, phosphazenes such as poly [di (carboxyratphenoxy) phosphazene] (PCPP) as described in references 162 and 163 may be used.</p><p num="0536"> (L. Muramyl peptide) Examples of muramyl peptides suitable for use as an adjuvant in the present invention are N-acetyl-muramil-L-threonyl-D-isoglutamine (thr-MDP), N-acetyl-normuramil-L-alanyl-D-iso. Glutamine (nor-MDP), and N-Acetyl Muramyl-L-Alanyl-D-Isoglutamine-L-Alanine-2- (1'-2'-Dipalmityl-sn-Glycero-3-Hydroxyphosphoryloxy) -Ethylamine Includes (MTP-PE).</p><p num="0537"> (M. imidazole quinolone compound) Examples of imidazoquinolone compounds suitable for use as adjuvants in the present invention are imiquimod (R-837) [164, 165], reshikimod (R-848) [166] and their analogs, and their analogs. Contains salts (eg, hydrochlorides). Further details about the immunostimulatory imidazoquinoline can be found in references 167-171.</p><p num="0538"> (N. Replace urea) Substituted ureas useful as adjuvants are compounds of formula I, II or III, as defined in reference 172, or salts thereof:</p><p num="0539"><chemistry num="3"><img id="000004" he="52" wi="136" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>For example, "ER803058", "ER803732", "ER804053", "ER804058", "ER804059", "ER804442", "ER804680", "ER804764", "ER803022" or "ER804057", for example:</p><p num="0540"><chemistry num="4"><img id="000005" he="105" wi="124" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>including.</p><p num="0541"> (O. Further adjuvant) Additional adjuvants that can be used in the present invention include:</p><p num="0542"> Aminoalkyl glucosaminidoric acid derivatives such as .RC-529 [173, 174].</p><p num="0543"> Cyclic diguanylate ("c-di-GMP") [175], which has been reported as a useful adjuvant for the S. aureus vaccine.</p><p num="0544"> A thiosemicarbazone compound such as that disclosed in reference 176. Methods for formulation, production and screening for active compounds are also described in reference 176. Thiosemicarbazone is particularly effective in stimulating human peripheral blood mononuclear cells for the production of cytokines such as TNF-α.</p><p num="0545"> Triptan compounds such as those disclosed in reference 177. Methods for formulation, production and screening for active compounds are also described in reference 177. Thiosemicarbazone is particularly effective in stimulating human peripheral blood mononuclear cells for the production of cytokines such as TNF-α.</p><p num="0546"> . (a) Isatrabin (ANA-245; 7-thia-8-oxoguanosine):</p><p num="0547"><chemistry num="5"><img id="000006" he="37" wi="51" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>And their prodrugs; (b) ANA975; (c) ANA-025-1; (d) ANA380; (e) The compound loxolibin (7-allyl-8-oxoguanosine) disclosed in references 178-180 [ Nucleoside analogs such as 181].</p><p num="0548"> -Acylpiperazine compound, indoldione compound, Tetrahydra isoquinoline (THIQ) compound, benzocyclodione compound, aminoazavinyl compound, aminobenzimidazoline quinolinone (ABIQ) compound [183, 184], Hydrapthalamide compound, Reference 182, which includes benzophenone compounds, isoxazole compounds, sterol compounds, quinazilinone compounds, pyrrol compounds [185], anthraquinone compounds, quinoxalin compounds, triazine compounds, pyrazalopyrimidine compounds and benzazole compounds [186]. The disclosed compound.</p><p num="0549"> .TLR4 antagonist A lipid-containing compound linked to a phosphate-containing acyclic skeleton, such as E5564 [187, 188].</p><p num="0550"> Polyethylene polymer [189, 190] or other polyethylene oxide-piperazine derivatives.</p><p num="0551"> -Methylinosin 5'-1 phosphate ("MIMP") [191].</p><p num="0552"> ·formula:</p><p num="0553"><chemistry num="6"><img id="000007" he="21" wi="51" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>(In the formula, R is selected from the group containing hydrogen, linear or branched, unsaturated or substituted, saturated or unsaturated acyls, alkyls (eg, cycloalkyls), alkenyls, alkynyls and aryl groups). Polyhydroxylated pyrrolididine compounds [192], such as those having, or pharmaceutically acceptable salts or derivatives thereof. Examples include, but are not limited to, casalin, casalin-6-α-D-glucopyranose, 3-epi-casalin, 7-epi-casalin, 3,7-di-epi-casalin and the like.</p><p num="0554"> .α-Glycosylceramide [193 ~ 200] (eg α-galactosylceramide), phytosphingosine-containing α-glycosylceramide, OCH, KRN7000 [(2S, 3S, 4R) -1-O- (α-D-galactosylceramide) CD1d ligands such as syl) -2- (N-hexacosanoylamino) -1,3,4-octadecantriol], CRONY-101, 3''-O-sulfo-galactosylceramide.</p><p num="0555"> Gamma inulin [201] or its derivatives, such as algamulin.</p><p num="0556"><chemistry num="7"><img id="000008" he="46" wi="103" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry> (Combination of adjuvant) The present invention may also include one or more combinations of the adjuvants identified above. For example, the following adjuvant compositions may be used in the present invention: (1) saponin and oil-in-water emulsion [202]; (2) saponin (eg QS21) + non-toxic LPS derivative (eg 3dMPL) [203]; (3) Saponin (eg QS21) + non-toxic LPS derivative (eg 3dMPL) + cholesterol; (4) Saponin (eg QS21) + 3dMPL + IL-12 (optionally + sterol) [204]; (5) 3dMPL, For example, in combination with QS21 and / or oil-in-water emulsion [205]; (6) 10% squalane, microfluidized to a submicron emulsion or vortexed to produce an emulsion of larger particle size, 0.4% Tween80^TM, 5% Pluronic-block polymer L121 and SAF containing thr-MDP, (7) from 2% squalene, 0.2% Tween80 and monophosphoryl lipid A (MPL), trehalose dimycholic acid (TDM) and cell wall skeleton (CWS) One or more bacterial cell wall components from the group, preferably MPL + CWS (Detox)^TM) Containing Ribi^TMAn adjuvant system (RAS) (Ribi Immunochem); and (8) a non-toxic derivative of one or more inorganic salts (eg aluminum salts) + LPS (eg 3dMPL).</p><p num="0557"> Other substances that act as immunostimulants are disclosed in Chapter 7 of reference 82.</p><p num="0558"> The use of aluminum hydroxide and / or aluminum phosphate adjuvant is particularly preferred, and the antigen is generally adsorbed on these salts. Calcium phosphate is another preferred adjuvant. Other preferred adjuvant combinations include combinations of Th1 and Th2 adjuvants such as CpG and alum, or resikimod and alum. A combination of aluminum phosphate and 3dMPL may be used.</p><p num="0559"> The compositions of the present invention can elicit both a cell-mediated immune response and a humoral immune response. This immune response preferably induces long-lasting (eg, neutralizing) antibodies and cell-mediated immunity that can respond rapidly upon exposure to Streptococcus pneumoniae.</p><p num="0560"> Two types of T cells, namely CD4 and CD8 cells, are generally thought to be required to initiate and / or enhance cell-mediated and humoral immunity. CD8 T cells can express the CD8 co-receptor and are commonly referred to as cytotoxic T lymphocytes (CTLs). CD8 T cells can recognize or interact with the antigen presented on MHC class I molecules.</p><p num="0561"> CD4 T cells can express the CD4 coreceptor and are commonly referred to as T helper cells. CD4 T cells can recognize antigenic peptides bound to MHC class II molecules. By interacting with MHC class II molecules, CD4 cells can secrete factors such as cytokines. These secreted cytokines can activate B cells, cytotoxic T cells, macrophages and other cells that participate in the immune response. Helper T cells or CD4 + cells can be further subdivided into two functionally distinct subsets, the TH1 and TH2 phenotypes, which differ in their cytokine and effector function.</p><p num="0562"> Activated TH1 cells enhance cell-mediated immunity (including increased production of antigen-specific CTLs) and are therefore of particular value in response to intracellular infections. Activated TH1 cells can secrete one or more of IL-2, IFN-γ and TNF-β. The TH1 immune response can result in a local inflammatory response by activating macrophages, NK (natural killer) cells and CD8 cytotoxic T cells (CTL). The TH1 immune response may also act to enhance the immune response by stimulating B and T cell proliferation with IL-12. TH1-stimulated B cells can secrete IgG2a.</p><p num="0563"> Activated TH2 cells enhance antibody production and are therefore of value in response to extracellular infection. Activated TH2 cells can secrete one or more of IL-4, IL-5, IL-6 and IL-10. The TH2 immune response can result in the production of IgG1, IgE, IgA and memory B cells for future defense.</p><p num="0564"> Immune response enhancement can include one or more of TH1 immune response enhancements and TH2 immune response enhancements.</p><p num="0565"> The TH1 immune response is an increase in CTL, an increase in one or more of the cytokines associated with the TH1 immune response (eg IL-2, IFN-γ and TNF-β), an increase in activated macrophages, an increase in NK activity, or IgG2a. Can include one or more of the increased production of. Preferably, the enhancement of the TH1 immune response comprises an increase in IgG2a production.</p><p num="0566"> The TH1 immune response can be evoked with a TH1 adjuvant. TH1 adjuvants generally elicit increased levels of IgG2a production compared to immunization with antigens without adjuvant. Suitable TH1 adjuvants for use in the present invention may include, for example, saponin formulations, virus-like and virus-like particles, non-toxic derivatives of Gut microbiota lipopolysaccharide (LPS), immunostimulatory oligonucleotides. Immunostimulatory oligonucleotides, such as oligonucleotides containing CpG motifs, are preferred TH1 adjuvants for use in the present invention.</p><p num="0567"> The TH2 immune response is an increase in one or more of the cytokines associated with the TH2 immune response (eg IL-4, IL-5, IL-6 and IL-10), or the production of IgG1, IgE, IgA and Memory B cells. It can include one or more of the increases. Preferably, the enhancement of the TH2 immune response comprises an increase in IgG1 production.</p><p num="0568"> The TH2 immune response can be evoked with a TH2 adjuvant. TH2 adjuvants generally elicit increased levels of IgG1 production compared to immunization with antigens without adjuvant. Suitable TH2 adjuvants for use in the present invention include, for example, inorganic-containing compositions, oily emulsions and ADP ribosylation toxins and detoxifying derivatives thereof. Inorganic-containing compositions such as aluminum salts are preferred TH2 adjuvants for use in the present invention.</p><p num="0569"> Preferably, the invention comprises a composition comprising a combination of a TH1 adjuvant and a TH2 adjuvant. Preferably, such a composition elicits an enhanced TH1 and enhanced TH2 response, i.e., an increased production of both IgG1 and IgG2a production compared to immunization without an adjuvant. .. Even more preferably, a composition comprising a combination of a TH1 adjuvant and a TH2 adjuvant is compared to an immunization with a single adjuvant (ie, an immunization with the TH1 adjuvant alone or an immunization with the TH2 adjuvant alone). ), Causes an increase in TH1 immune response and / or an increase in TH2 immune response.</p><p num="0570"> The immune response may be one or both of the TH1 and TH2 responses. Preferably, the immune response results in enhanced TH1 response and / or enhanced TH2 response.</p><p num="0571"> The enhancement of the immune response can be one or both of a systemic immune response and a mucosal immune response. Preferably, the immune response results in enhanced systemic immune response and / or enhanced mucosal immune response. Preferably, the mucosal immune response is a TH2 immune response. Preferably, the mucosal immune response comprises increased production of IgA.</p><p num="0572"> S. aureus infection can affect different areas of the body, so the compositions of the present invention may be prepared in different forms. For example, the composition may be prepared as an injectable, either as a liquid solution or as a suspension. Solid forms suitable for dissolution or suspension in liquid vehicles prior to injection can also be prepared (eg, lyophilized compositions or spray lyophilized compositions). The composition may be prepared for surface administration, for example as an ointment, cream or powder. The composition may be prepared for oral administration, eg, as a tablet or capsule, as a spray, or as a syrup (optionally flavored). The composition may be prepared for pulmonary administration, for example as an inhalant with a fine powder or spray. The composition may be prepared as a suppository or vaginal suppository. The composition may be prepared for nasal, ear or ocular administration, eg as a drop. The composition may be in the form of a kit designed so that the combination composition is reconstituted immediately prior to administration to a patient. Such a kit may include one or more antigens in liquid form and one or more lyophilized antigens.</p><p num="0573"> If the composition is instantly prepared prior to use (eg, if the ingredients are in lyophilized form) and is a kit, the kit may contain two vials, but with one ready-filled syringe. It may include one vial and the contents of the syringe are used to reactivate the contents of the vial prior to injection.</p><p num="0574"> The immunogenic composition used as a vaccine comprises an immunologically effective amount of the antigen (s) and optionally any other component. By "immunologically effective amount", it means that administering that amount to an individual, either as a single dose or as part of a series, is effective for treatment or prophylaxis. This amount is desired, the health and physical condition of the individual being treated, the age, the taxon of the individual being treated (eg, non-human primates, primates, etc.), the ability of the individual's immune system to synthesize antibodies. It depends on the degree of protection, vaccine prescription, treatment physician's assessment of the medical condition, and other relevant factors. This amount is expected to be in a relatively wide range that can be determined by routine testing. If more than one antigen is included in the composition, the two antigens may be present at the same or different doses from each other.</p><p num="0575"> As mentioned above, the composition may include a thermoprotectant, which component may be particularly useful in adjuvanted compositions, especially those containing an inorganic adjuvant such as an aluminum salt. As described in Reference 206, the liquid thermoprotectant may, in addition to the aqueous vaccine composition, lower its freezing point, eg, lowering the freezing point below 0 ° C. Therefore, although the composition is below 0 ° C, it can be stored above its freezing point and can inhibit temperature degradation. Thermoprotectants can also allow the composition to freeze while protecting the inorganic salt adjuvant from agglutination or sedimentation after freezing and thawing, allowing the composition to freeze at elevated temperatures, eg, temperatures above 40 ° C. It can also be protected. The starting aqueous vaccine and the liquid thermoprotectant may be mixed such that the liquid thermoprotectant forms 1-80% by volume of the final mixture. A suitable thermoprotectant should be safe for human administration, readily mismixable / soluble in water, and not damaging other components (eg, antigens and adjuvants) in the composition. Examples include glycerin, propylene glycol and / or polyethylene glycol (PEG). Suitable PEGs may have an average molecular weight in the range of 200-20,000 Da. In a preferred embodiment, polyethylene glycol can have an average molecular weight of about 300 Da (PEG-300).</p><p num="0576"> The present invention provides an immunogenic composition comprising (i) one or more antigens selected from the first, second, third or fourth antigen group and (ii) a thermoprotectant. This composition is formed by (i) mixing an aqueous composition containing one or more antigens selected from the first, second, third or fourth antigen group with a temperature protectant (ii). You can. The mixture may then be stored, for example, below 0 ° C, 0-20 ° C, 20-35 ° C, 35-55 ° C or higher. It may be stored in liquid or frozen form. The mixture may be lyophilized. The composition is instead a dry composition comprising (i) one or more antigens selected from the first, second, third or fourth antigen group, and (ii) a liquid composition comprising a temperature protectant. It may be formed by mixing with. Therefore, component (ii) can be used to reconstruct component (i).</p><p num="0577"> (Treatment method and administration of vaccine) The invention also provides a method of enhancing an immune response in a mammal, comprising the step of administering an effective amount of the composition of the invention. The immune response is preferably defensive, preferably with antibody and / or cell-mediated immunity. The method can enhance the booster immune response.</p><p num="0578"> The invention also provides at least two antigens of the invention for use in combination as pharmaceuticals for use, for example in enhancing an immune response in mammals.</p><p num="0579"> The invention also provides the use of at least two antigens of the invention in the manufacture of pharmaceuticals to enhance an immune response in mammals.</p><p num="0580"> By enhancing the immune response in mammals by these uses and methods, mammals can be protected against S. aureus infections, including nosocomial infections. More specifically, mammals can be protected against skin infections, pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome and / or sepsis.</p><p num="0581"> The present invention is a kit containing the first component and the second component, and neither the first component nor the second component is the above-mentioned composition of the present invention, but the first component and the second component are combined and described above. Also provided are kits capable of providing the compositions of the present invention. The kit may further include a third component, including one or more of the following: instructions for use, syringe or other delivery device, adjuvant or pharmaceutically acceptable formulation solution.</p><p num="0582"> The present invention also provides a delivery device pre-filled with the immunogenic composition of the present invention.</p><p num="0583"> Mammals are preferably humans. If the vaccine is prophylactic, the human is preferably a child (eg, infant or infant) or teenager, and if the vaccine is therapeutic, the human is preferably a teenager or adult. Vaccines intended for pediatric use may be administered to adults, for example to assess safety, dosage, immunogenicity, and the like. Other mammals that can be usefully immunized according to the present invention are cows, dogs, horses and pigs.</p><p num="0584"> One way to confirm the efficacy of a therapeutic procedure is to monitor S. aureus infection after administration of the compositions of the invention. One method for confirming the efficacy of prophylactic treatment is for systemic (eg, monitoring levels of IgG1 and IgG2a production) and / or mucosa (eg, monitoring levels of IgA production) for antigens in the compositions of the invention. Includes monitoring the immune response after administration of the composition. Typically, the antigen-specific serum antibody response is determined after immunization but before the challenge, while the antigen-specific mucosal antibody response is determined after immunization and after the challenge.</p><p num="0585"> Another method for assessing the immunogenicity of the compositions of the invention is to recombinantly express the protein to screen the patient's serum or mucosal secretions by immunoblot and / or microarray. A positive reaction between the protein and the patient sample indicates that the patient has initiated an immune response to the protein in question. This method may be used to identify immunodominant antigens and / or epitopes within the antigen.</p><p num="0586"> The efficacy of the vaccine composition can also be determined in vivo by challenging animal models of S. aureus infection, such as guinea pigs or mice, with the vaccine composition. In particular, there are three useful animal models for the study of S. aureus infections, namely (i) mouse abscess model [207], (ii) mouse lethal infection model [207] and (iii). Mouse pneumonia model [208]. The abscess model observes an abscess in the mouse kidney after an intravenous challenge. The lethal infection model observes the number of mice that survive after infecting a normally lethal dose of S. aureus by the intravenous or intraperitoneal route. The pneumonia model also observes survival, but uses intranasal infection. Useful vaccines may be effective in one or more of these models. For example, in some clinical situations, it may be desirable to protect against pneumonia without the need to prevent blood diffusion or promote opsonization. In other situations, it may be primarily desired to prevent spread by the blood. Different antigens and combinations of different antigens can contribute to different aspects of an effective vaccine.</p><p num="0587"> The compositions of the present invention are generally administered directly to the patient. Direct delivery can be parenteral injection (eg subcutaneous, intraperitoneal, intravenous, intramuscular or tissue interstitial space), or rectal, oral (eg tablet, spray), vaginal, superficial, transdermal or It may be achieved by mucosal administration such as transcutaneous, intranasal, eye, ear, lung or other mucosal administration.</p><p num="0588"> The present invention may be used to elicit systemic and / or mucosal immunity, preferably enhanced systemic and / or mucosal immunity.</p><p num="0589"> Preferably, enhanced systemic and / or mucosal immunity is reflected in enhanced TH1 and / or TH2 immune responses. Preferably, the enhanced immune response comprises increased production of IgG1 and / or IgG2a and / or IgA.</p><p num="0590"> Dosing can be by single dose planning or multiple dose planning. Multiple doses may be used in the primary and / or booster immunization scheme. In multiple dose planning, different doses may be given by the same or different routes, such as parenteral primary and mucosal boosters, mucosal primary and parenteral boosters, and the like. Multiple doses are typically given at least 1 week apart (eg, about 2 weeks, about 3 weeks, about 4 weeks, about 6 weeks, about 8 weeks, about 10 weeks, about 12 weeks, about 16). Weeks etc.).</p><p num="0591"> Vaccines prepared according to the present invention may be used to treat both children and adults. Thus, human patients may be less than 1 year old, 1-5 years old, 5-15 years old, 15-55 years old or at least 55 years old. Preferred patients to receive the vaccine are the elderly (eg 50, 60, preferably 65), the young (eg 5), inpatients, health care workers, military and military personnel, pregnant women. , Chronic sick or immunocompromised. However, vaccines are not only suitable for these groups and may be used more commonly in populations.</p><p num="0592"> Vaccines produced according to the present invention can be used substantially simultaneously with other vaccines (eg, during the same medical consultation or visit to a medical professional or vaccination center), such as influenza vaccine, measles vaccine, epidemic parotid gland. Flame vaccine, rash vaccine, MMR vaccine, varicella vaccine, MMRV vaccine, diphtheria vaccine, tetanus vaccine, pertussis vaccine, DTP vaccine, conjugate H. influenzae b vaccine, inactivated poliovirus vaccine, hepatitis B virus vaccine, medullary membrane It may be administered to the patient substantially simultaneously with the flame bacterium conjugate vaccine (for example, 4-valent AC-W135-Y vaccine), RS virus vaccine and the like. Additional non-staphylococcal vaccines suitable for co-administration may include one or more antigens listed on pages 33-46 of reference 51.</p><p num="0593"> (Nucleic acid immunization) The immunogenic composition described above comprises a polypeptide antigen from S. aureus. However, in all cases, polypeptide antigens can be replaced with nucleic acids (typically DNA) encoding these polypeptides, resulting in compositions, methods and uses based on nucleic acid immunization. Nucleic acid immunization is now an advanced field (see references 209-216, for example).</p><p num="0594"> The nucleic acid encoding the immunogen is expressed in vivo after being delivered to the patient, and the expressed immunogen then stimulates the immune system. The active ingredient typically takes the form of a nucleic acid vector comprising (i) a promoter, (ii) a sequence encoding an immunogen operably linked to the promoter, and optionally (iii) a selectable marker. A preferred vector may further include (iv) an origin of replication and a transcription terminator downstream of (v) (ii) and operably linked to (ii). In general, (i) and (v) are for eukaryotes and (iii) and (iv) are for prokaryotes.</p><p num="0595"> Preferred promoters are, for example, viral promoters from cytomegalovirus (CMV). The vector may include a transcriptional regulatory sequence (eg, an enhancer) in addition to the promoter, which interacts functionally with the promoter. Preferred vectors include pre-early CMV enhancers / promoters, and more preferred vectors also include CMV intron A. The promoter operably links to the downstream sequence encoding the immunogen so that the expression of the sequence encoding the immunogen is under the control of the promoter.</p><p num="0596"> When using a marker, it preferably functions within a microbial host (eg, within a prokaryote, within a bacterium, within yeast). The marker is preferably a prokaryotic selectable marker (eg, transcribed under the control of a prokaryotic promoter). For convenience, a typical marker is an antibiotic resistance gene.</p><p num="0597"> The vectors of the invention are preferably self-replicating episomes such as plasmids or extrachromosomal vectors.</p><p num="0598"> The vector of the present invention preferably comprises an origin of replication. The origin of replication is active in the prokaryote, but is preferably not active in the eukaryote.</p><p num="0599"> Thus, preferred vectors include prokaryotic markers for vector selection, prokaryotic origins of replication, and eukaryotic promoters that drive transcription of sequences encoding immunogens. The vector is thus (a) amplified and selected in the prokaryotic host without expressing the polypeptide, and (b) expressed in the eukaryotic host without being amplified. This configuration is ideal for nucleic acid immunization vectors.</p><p num="0600"> The vector of the present invention may contain a eukaryotic transcription terminator sequence downstream of the coding sequence. This can increase the transcription level. If the coding sequence does not have its own, the vector of the invention preferably comprises a polyadenylation sequence. The preferred polyadenylation sequence is from bovine proliferative hormone.</p><p num="0601"> The vector of the present invention may contain a multicloning site.</p><p num="0602"> In addition to the sequences encoding immunogens and markers, the vector may include a second eukaryotic coding sequence. The vector can also allow translation of the second eukaryotic polypeptide from the same transcript as the immunogen by including the IRES upstream of the second sequence above. Alternatively, the immunogen coding sequence may be downstream of the IRES.</p><p num="0603"> Vectors of the invention may include unmethylated CpG motifs, eg, unmethylated DNA sequences that commonly carry cytosine before guanosine, sandwiched between two 5'purines and two 3'pyrimidines. In these unmethylated forms, these DNA motifs have proven to be potent stimulants of several types of immune cells.</p><p num="0604"> The vector may be delivered in a targeted fashion. Receptor-mediated DNA delivery techniques are described, for example, in References 217-222. The therapeutic composition containing the nucleic acid is administered with DNA in the range of about 100 ng to about 200 mg for topical administration in the gene therapy protocol. DNA concentration ranges of about 500 ng to about 50 mg, about 1 μg to about 2 mg, about 5 μg to about 500 μg, and about 20 μg to about 100 μg can also be used during gene therapy protocols. Factors such as the method of action (eg, for enhancing or inhibiting the level of the encoded gene product) and the potency of transformation and expression affect the dose required for ultimate potency, consideration. It is a matter to be done. If higher expression is desired over a larger area of tissue, a higher amount of vector, or the same amount re-administered in a continuous dosing protocol, or several doses to various adjacent or close tissue parts, may be used. May be required to bring about positive therapeutic outcomes. In all cases, routine experiments in clinical trials determine a specific range of optimal therapeutic effects.</p><p num="0605"> The vector can be delivered using a gene delivery vehicle. The gene delivery vehicle can be of viral or non-viral origin (generally see references 223-226).</p><p num="0606"> Virus-based vectors for delivery of the desired nucleic acid and expression in the desired cells are well known in the art. Exemplary virus-based vehicles are, but are not limited to, recombinant retroviruses (eg, References 227-237), alpha virus-based vectors (eg, Sindbis virus vector, Semuliki forest virus (ATCC VR-67; ATCC)). VR-1247), Ross River virus (ATCC VR-373; ATCC VR-1246) and Venezuelan encephalitis virus (ATCC VR-923; ATCC VR-1250; ATCC VR1249; ATCC VR-532); Chimeras may also be used), including poxvirus vectors (eg, vaccinia, poultry, canarypox, modified vaccinia Ankara, etc.), adenovirus vectors, and adeno-associated virus (AAV) vectors (see, eg, references 238-243). I want). Administration of DNA [244] linked to killed adenovirus can also be used.</p><p num="0607"> Polycation linked DNA [eg 244], ligand linked DNA [245], eukaryotic cell delivery vehicle cells [eg 246-250] linked or not linked solely to inactivated adenovirus, but not limited to them. And non-viral delivery vehicles and methods involving nuclear charge neutralization or fusion with cell membranes can also be used. Bare DNA can also be used. An exemplary method of introducing naked DNA is described in references 251 and 252. Liposomes that can act as gene delivery vehicles (eg, immunoliposomes) are described in references 253 to 257. Further approaches are described in references 258 and 259.</p><p num="0608"> Further non-viral delivery suitable for use includes mechanical delivery systems such as the approach described in reference 259. In addition, the coding sequence and the product of its expression can be delivered by deposition of photopolymerized hydrogel material or by the use of ionizing radiation [eg, References 260 and 261]. Other conventional methods for gene transfer that can be used to deliver the coding sequence include, for example, the use of a hand-held gene transfer particle gun [262] or the transferred gene. Includes the use of ionizing radiation to activate [260 and 261].</p><p num="0609"> Delivery DNA using PLG {poly (lactide-co-glycolide)} microparticles is a particularly preferred method, for example by adsorption to microparticles, where these microparticles are optionally negatively charged surfaces (eg SDS). Treated with) or to have a positively charged surface (treated with a cationic detergent such as CTAB).</p><p num="0610"> (S.epidermidis) Although the present invention focuses on S. aureus, we also recognize that the sta006 and sta011 antigens have homology to S. epidermidis. For example, SEQ ID NO: 234 is an "iron (Fe + 3) ABC superfamily ATP binding cassette transporter, binding protein" from the S. epidermidis M23864: W1 strain, which has 73% identity with SEQ ID NO: 42 (sta006). And SEQ ID NO: 235 is a "estimated lipoprotein" from the S. epidermidis RP62A strain, which has 67% identity with SEQ ID NO: 47 (sta011).</p><p num="0611"> S. epidermidis is usually present on human skin and can occasionally cause illness. Infections are usually associated with medical devices such as catheters and are the cause of nosocomial infections. The results disclosed herein for sta006 and sta011 against S. aureus suggest that homologous proteins in S. epidermidis may be useful for immunization against this pathogen.</p><p num="0612"> The present invention (i) (a) 50% or more identity with SEQ ID NO: 234 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%) , 95%, 96%, 97%, 98%, 99%, 99.5% or more) and / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 234 (where "n" is , 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more) Polypeptide containing an amino acid sequence containing, And / or(ii) (a) 50% or more identity with SEQ ID NO: 235 (eg 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%) , 95%, 96%, 97%, 98%, 99%, 99.5% or more) and / or (b) at least the "n" contiguous amino acid fragment of SEQ ID NO: 235 (where "n" is , 7 or more (eg 8, 10, 12, 14, 16, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250 or more) Polypeptide containing an amino acid sequence containing To provide an immunogenic composition comprising.</p><p num="0613"> The composition may also include an adjuvant. These compositions are particularly useful for immunizing mammals (including humans) against S. epidermidis infection.</p><p num="0614"> The preferred fragment of (b) comprises an epitope from SEQ ID NO: 234 or 235, respectively. Other preferred fragments include one or more amino acids from the C-terminus of SEQ ID NO: 234/235 (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 and above) and / Or deletes one or more amino acids (eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25 or more) from the N-terminus, but SEQ ID NO: 234 It carries at least one epitope of / 235.</p><p num="0615"> More generally, the present invention provides the use of sta006 and / or sta011 homologues from any Staphylococcus species to immunize mammals against that species.</p><p num="0616"> (antibody) Antibodies to the S. aureus antigen can be used for passive immunity. Thus, the present invention provides antibodies that are specific for the antigens of the first, second, third or fourth antigen group. The present invention also provides the use of such antibodies in treatment. The present invention also provides for the use of such antibodies in the manufacture of pharmaceuticals. The invention also provides a method of treating a mammal, comprising the step of administering an effective amount of the antibody of the invention. As mentioned above for immunogenic compositions, these methods and uses make it possible to protect mammals against S. aureus infection.</p><p num="0617"> The term "antibody" includes intact immunoglobulin molecules and fragments thereof that can bind antigens. These are hybrid (chimeric) antibody molecules [263, 264]; F (ab') 2 and F (ab) fragments and Fv molecules; non-covalently bound heterodimers [265, 266]; single chain Fv molecules (sFv) [ 267]; Dimer and trimmer antibody fragment constructs; Minibody [268, 269]; Humanized antibody molecules [270-272]; as well as any functional fragments obtained from such molecules, as well as idiomatic such as phage display. Contains antibodies obtained by non-processes. Preferably, the antibody is a monoclonal antibody. Methods for obtaining monoclonal antibodies are well known in the art. Humanized or fully human antibodies are preferred.</p><p num="0618"> (General) The practice of the present invention uses conventional methods of chemistry, biochemistry, molecular biology, immunology and pharmacology within the scope of the art, unless otherwise stated. Such techniques are described in detail in the literature. See, for example, references 273-280.</p><p num="0619"> The "GI" numbering is used above. A GI number or "GenInfo identifier" is a series of numbers that are continuously assigned to each recorded array processed by NCBI when an array is added to the database. The GI number has no similarity to the accession number of the recorded sequence. When the array is updated (for example, to modify it or to add more annotation or information), it will be given a new GI number. Therefore, the array associated with the given GI number is never changed.</p><p num="0620"> When the present invention relates to an "epitope", this epitope may be a B cell epitope and / or a T cell epitope. Such epitopes can be empirically identified (eg, using PEPSCAN [281, 282] or similar methods), or this can be expected (eg, Jameson-Wolf antigen index [283], matrix-based approach [ 284], MAPITOPE [285], TEPITOPE [286, 287], Neural Network [288], OptiMer &amp; EpiMer [289, 290], ADEPT [291], Tsites [292], Hydrophilic [293], Antigen Index [294] or (Using the methods disclosed in References 295 to 299, etc.). Epitopes are parts of an antigen that are recognized and bind to an antibody or T cell receptor by the antigen binding site, which can also be referred to as "antigen determinants."</p><p num="0621"> When the antigen "domain" is removed, this may include the removal of signal peptides, cytoplasmic domains, transmembrane domains, extracellular domains and the like.</p><p num="0622"> The term "comprising" includes "including" and "consisting", for example, a composition "comprising" containing X may consist only of X or something. It may include additional ones, eg X + Y.</p><p num="0623"> The term "about" with respect to the number x is optional and means, for example, x ± 10%.</p><p num="0624"> References to percentage sequence identity between two amino acid sequences mean that, when aligned, that percentage of amino acids is the same in the comparison of the two sequences. This alignment and percent homology or sequence identity can be determined using software programs known in the art, such as those described in Section 7.7.18 of reference 300. Preferred alignments are determined by the Smith-Waterman homology search algorithm with 12 gap open penalties and 2 gap extension penalties, and an affine gap search with 62 BLOSUM matrices. The Smith-Waterman homology search algorithm is disclosed in reference 301. Therefore, the present invention provides the following items:(Item 1)An immunogenic composition comprising a combination of antigens, wherein the combination is (1) sta006 antigen; (2) sta011 antigen; (3) esxA antigen; (4) esxB antigen; (5) hla antigen; (6) ) EbpS antigen; (7) efb antigen; (8) emp antigen; (9) esaC antigen; (10) coA antigen; (11) eap antigen; (12) FnBA antigen; (13) FnBB antigen; (14) ebhA Antigens; (15) hlgB antigens; (16) hlgC antigens; (17) isdA antigens; (18) isdB antigens; (19) isdC antigens; (20) isdG antigens; (21) isdH antigens; (22) isdI antigens; (23) lukD antigen; (24) lukE antigen; (25) lukF antigen; (26) lukS antigen; (27) nuc antigen; (28) sasA antigen; (29) sasB antigen; (30) sasC antigen; (31) ) SasD antigen; (32) sasF antigen; (33) sdrC antigen; (34) sdrD antigen; (35) sdrE2 antigen; (36) spa antigen; (37) clfA antigen; (38) clfB antigen; (39) sta001 Antigen; (40) sta002 antigen; (41) sta003 antigen; (42) sta004 antigen; (43) sta005 antigen; (44) sta007 antigen; (45) sta008 antigen; (46) sta009 antigen; (47) sta010 antigen; (48) sta012 antigen; (49) sta013 antigen; (50) sta014 antigen; (51) sta015 antigen; (52) sta016 antigen; (53) sta017 antigen; (54) sta018 antigen; (55) sta019 antigen; (56) ) Sta020 antigen; (57) sta021 antigen; (58) sta022 antigen; (59) sta023 antigen; (60) sta024 antigen; (61) sta025 antigen; (62) sta026 antigen; (63) sta027 antigen; (64) sta028 Antigen; (65) sta029 antigen; (66) sta030 antigen; (67) sta031 antigen; (68) sta032 antigen; (69) sta033 antigen; (70) sta034 antigen;(71) sta035 antigen; (72) sta036 antigen; (73) sta037 antigen; (74) sta038 antigen; (75) sta039 antigen; (76) sta040 antigen; (77) sta041 antigen; (78) sta042 antigen; (79) )sta043 antigen;(80)sta044 antigen;(81)sta045 antigen;(82)sta046 antigen;(83)sta047 antigen;(84)sta048 antigen;(85)sta049 antigen;(86)sta050 antigen;(87)sta051 Antigen; (88) sta052 antigen; (89) sta053 antigen; (90) sta054 antigen; (91) sta055 antigen; (92) sta056 antigen; (93) sta057 antigen; (94) sta058 antigen; (95) sta059 antigen; (96) sta060 antigen; (97) sta061 antigen; (98) sta062 antigen; (99) sta063 antigen; (100) sta064 antigen; (101) sta065 antigen; (102) sta066 antigen; (103) sta067 antigen; (104) )sta068 antigen;(105)sta069 antigen;(106)sta070 antigen;(107)sta071 antigen;(108)sta072 antigen;(109)sta073 antigen;(110)sta074 antigen;(111)sta075 antigen;(112)sta076 Antigen; (113) sta077 antigen; (114) sta078 antigen; (115) sta079 antigen; (116) sta080 antigen; (117) sta082 antigen; (118) sta083 antigen; (119) sta084 antigen; (120) sta085 antigen; (121) sta086 antigen; (122) sta087 antigen; (123) sta088 antigen; (124) sta089 antigen; (125) sta090 antigen; (126) sta091 antigen; (127) sta092 antigen; (128) sta093 antigen; (129) ) sta094 antigen; (130) sta095 antigen; (131) sta096 antigen; (132) sta097 antigen; (133) sta098 antigen;(134) sta099 antigen; (135) sta100 antigen; (136) sta101 antigen; (137) sta102 antigen; (138) sta103 antigen; (139) sta104 antigen; (140) sta105 antigen; (141) sta106 antigen; (142) ) Sta107 antigen; (143) sta108 antigen; (144) sta109 antigen; (145) sta110 antigen; (146) sta111 antigen; (147) sta112 antigen; (148) sta113 antigen; (149) sta114 antigen; (150) sta115 Antigens; (151) sta116 antigens; (152) sta117 antigens; (153) sta118 antigens; (154) sta119 antigens; (155) sta120 antigens; (156) NW_6 antigens; (157) NW_9 antigens; (158) NW_10 antigens; Includes two or more antigens selected from the group consisting of (159) NW_7 antigen; (160) NW_8 antigen; (161) NW_2 antigen; (162) NW_1 antigen; (163) sta081 antigen; and (164) NW_5 antigen. Composition.And (164) A composition comprising two or more antigens selected from the group consisting of NW_5 antigens.And (164) A composition comprising two or more antigens selected from the group consisting of NW_5 antigens. (Item 2) Item 1. The item 1 comprises at least one antigen selected from numbers (3) to (38) and at least one antigen selected from numbers (1), (2) and (37) to (149). Composition. (Item 3) Numbers (37), (38), (8), (9), (3), (4), (5), (17), (18), (19), (31), (32), ( At least one antigen selected from 33), (34), (35) and (36), as well as (40), (1), (43), (2), (64), (96), ( The composition according to item 2, which comprises at least one antigen selected from 133) and (147). (Item 4) (1) clfA antigen; (2) clfB antigen; (3) sdrE2 antigen; (4) sdrC antigen; (5) SasF antigen; (6) emp antigen; (7) sdrD antigen; (8) spa antigen; (9) ) EsaC antigen; (10) esxA antigen; (11) esxB antigen; (12) sta006 antigen; (13) isdC antigen; (14) hla antigen; (15) sta011 antigen; (16) isdA antigen; (17) isdB Antigen; (18) The composition according to item 1, which comprises two or more antigens selected from the group consisting of sasF antigens. (Item 5) The composition according to item 1, which comprises two or more antigens selected from the group consisting of (1) esxA antigen; (2) esxB antigen; (3) sta006 antigen; (4) hla antigen; (5) sta011 antigen. .. (Item 6) A composition according to any one of the above items, wherein one or more of the antigens are adsorbed on an aluminum hydroxide adjuvant, and if desired, the composition comprises a histidine buffer. (Item 7) The composition according to any of the above items, further comprising one or more conjugates of (i) S. aureus exopolysaccharide and (ii) carrier protein. (Item 8) The composition according to any of the above items, further comprising one or more conjugates of (i) S. aureus capsular polysaccharide and (ii) carrier protein. (Item 9) Formula NH₂-A-{-X-L-}_n-B-COOH (In the formula, X is the S. aureus antigen.<chemistry num="9"><img id="000009" he="72" wi="147" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>It is an amino acid sequence of a staphylococcal antigen selected from the group consisting of L is an optional linker amino acid sequence, A is an optional N-terminal amino acid sequence, B is an optional C-terminal amino acid sequence, n is an integer greater than or equal to 2) Polypeptide. (Item 10) Contains the polypeptide according to item 9. (A) (i) S. aureus extracellular polysaccharide and (ii) one or more conjugates of carrier protein and / or One or more conjugates of (B) (i) S. aureus capsular polysaccharide and (ii) carrier protein An immunogenic composition further comprising. (Item 11) The above clfA antigen Can elicit an antibody that recognizes SEQ ID NO: 1 (a) Have at least 80% identity with SEQ ID NO: 1 and / or (b) Containing fragments of at least 7 consecutive amino acids of SEQ ID NO: 1 Contains amino acid sequence The composition or polypeptide according to any of the above items, wherein the fragment comprises an epitope from SEQ ID NO: 1. (Item 12) (a) Have at least 80% identity with SEQ ID NO: 151 and / or(b) Contains fragments of at least 7 consecutive amino acids from amino acids 1-97 of SEQ ID NO: 151 and at least 7 consecutive amino acids from amino acids 104-207 of SEQ ID NO: 151. A polypeptide containing an amino acid sequence, wherein the polypeptide can elicit an antibody that recognizes both a wild-type staphylococcal protein containing SEQ ID NO: 10 and a wild-type staphylococcal protein containing SEQ ID NO: 11. (Item 13) An immunogenic composition comprising the polypeptide of item 12, as well as one or more of (i) sta006 antigen; (ii) hla antigen; and / or (iii) sta011 antigen. (Item 14) The composition according to item 13, which comprises an adjuvant. (Item 15) Amino acids selected from SEQ ID NOs: 151, 152, 168, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 220, 221, 222, 223, 224, 237, 238, 241 A polypeptide containing an amino acid sequence having 80% or more identity with the sequence. (Item 16)SEQ ID NOs: 151, 152, 168, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 220, 221, 222, 223, 224, 237, 238, 241, 242, 243, A polypeptide containing an amino acid sequence selected from 244 and 245. (Item 17) A polypeptide comprising (a) a first sequence having 90% or more identity with SEQ ID NO: 218 and (b) a second sequence having 90% or more identity with SEQ ID NO: 219. A polypeptide in which the sequence and the second sequence are either directly linked or joined by an intervening amino acid sequence having less than 10 amino acids. (Item 18) A pharmaceutical composition comprising the polypeptide according to any one of items 12, 15, 16 or 17. (Item 19) A method of enhancing an immune response in a mammal, comprising the step of administering to the mammal an effective amount of the polypeptide or composition according to any of the above items. (Item 20) Nucleic acid encoding the polypeptide of item 9, 12, 15, 16 or 17.</p>

0625<figref num="1">FIG. 1 shows the post-challenge bacterial count (Log cfu / ml) of mice pre-immunized with the antigens described.</figref><figref num="2">Figures 2-4 show the post-challenge survival (%) of mice pre-immunized with various mixtures of antigens over a 14-day period. In Figure 2, the 6 groups from SA-10-a were group (i), group (iii) and group (iv), group (ii), IsdB, and negative controls from top to bottom on day 14. Is.</figref><figref num="3">In Figure 3, the 6 groups from SA-10-a were group (i), group (iii) and group (iv), group (ii), IsdB, and negative controls from top to bottom on day 14. Is. In Figure 3, the 6 groups from SA-10-b were group (iii), group (i), group (iv), group (ii) and IsdB, and negative controls from top to bottom on day 14. Is.</figref><figref num="4">In FIG. 4, the 6 groups from SA-14 are group (iv), group (ii), group (i), group (iii), negative control and IsdB from top to bottom on day 14.</figref><figref num="5">FIG. 5 shows four different doses after challenge of mice pre-immunized with various compositions (PBS negative control; IsdB antigen; and combination of "Combo-1" and "Combo-2" antigens of the invention). The data collected for mouse survival from the experiment is shown. Individual markers indicate the survival duration of individual mice, horizontal bars in each group indicate median survival duration, percentage numbers indicate survival 14 days after challenge, and the upper p-value is This is a t-test comparison of median survival duration between groups.</figref><figref num="6">Figure 6 shows 9 × 10 in an abscess model.⁶The number of colony forming units (cfu) in the mouse kidney after infection with the Newman strain of cfu is shown. The horizontal bars are the average per group, and the number below each group is the log reduction for the PBS control group.</figref><figref num="7A">FIG. 7 shows the bacterial count (log CFU / ml) in the kidney of mice in an abscess model experiment. Mice were challenged with the following strains: (A) MW2; (B) LAC; (C) Staph19; or (D) MU50. Each point is an individual animal and the bar indicates the median count per group. Mice were immunized as shown on the x-axis label.</figref><figref num="7B">FIG. 7 shows the bacterial count (log CFU / ml) in the kidney of mice in an abscess model experiment. Mice were challenged with the following strains: (A) MW2; (B) LAC; (C) Staph19; or (D) MU50. Each point is an individual animal and the bar indicates the median count per group. Mice were immunized as shown on the x-axis label.</figref><figref num="7C">FIG. 7 shows the bacterial count (log CFU / ml) in the kidney of mice in an abscess model experiment. Mice were challenged with the following strains: (A) MW2; (B) LAC; (C) Staph19; or (D) MU50. Each point is an individual animal and the bar indicates the median count per group. Mice were immunized as shown on the x-axis label.</figref><figref num="7D">FIG. 7 shows the bacterial count (log CFU / ml) in the kidney of mice in an abscess model experiment. Mice were challenged with the following strains: (A) MW2; (B) LAC; (C) Staph19; or (D) MU50. Each point is an individual animal and the bar indicates the median count per group. Mice were immunized as shown on the x-axis label.</figref><figref num="8">Figure 8 shows the increasing concentration of Ca.⁺⁺It shows the formation of Sta011 oligomers in the presence of ions. The number indicates the mM concentration,^*Indicates the presence of 50 mM EDTA.</figref><figref num="9-1">FIG. 9 shows IgG titers for (A) EsxAB, (B) Sta006, (C) Hla-H35L, and (D) Sta011. Each graph has 3 groups, and each group has a pair of bars. The bar on the right side of the pair shows pre-immunity IgG and the bar on the left side shows post-immunization IgG. Group 3 are the compositions used for immunization, from left to right, only the adjuvant-only negative control; Combo1 combination; and the associated antigen.</figref><figref num="9-2">FIG. 9 shows IgG titers for (A) EsxAB, (B) Sta006, (C) Hla-H35L, and (D) Sta011. Each graph has 3 groups, and each group has a pair of bars. The bar on the right side of the pair shows pre-immunity IgG and the bar on the left side shows post-immunization IgG. Group 3 are the compositions used for immunization, from left to right, only the adjuvant-only negative control; Combo1 combination; and the associated antigen.</figref><figref num="10">FIG. 10 shows the bacterial count values (log CFU / ml) in mice after challenge with the listed strains. Each point is an individual animal and the bar indicates the median CFU. The P values below the IsdB and Combo columns are comparisons to adjuvant-only controls.</figref><figref num="11">Figure 11 shows the area of the abscess (mm) in mice after the challenge with the Newman strain.²) Is shown.</figref><figref num="12">FIG. 12 shows the survival days of mice after challenge with four different strains, Newman (), ST-80 (), USA300-FPR3757 (Δ) or USA300-Lac (×) strains. Each point is an individual animal, the bar indicates median survival, and the number at the top indicates the percentage of animals that survive after 15 days. Mice received IsdB or Combo1 with aluminum hydroxide adjuvant only.</figref><figref num="13">FIG. 13 shows the median survival (days) of mice after the challenge. Mice were immunized with the antigens listed on the X-axis. Each point is an individual animal and bars indicate median survival. The number at the top indicates the percentage of animals that survive after 15 days.</figref>

0626(Form for carrying out the invention) (Selection of antigen) The S. aureus protein was selected for use as a vaccine component based on various criteria.

0627IsdA is a surface protein involved in iron uptake. It is detectable at high molecular weight (&gt; 250 kDa) in immunoblots of S. aureus whole cell lysates and cell mural fractions. In addition, the labeled anti-IsdA antibody revealed extracellular structure. These structures were observed under a variety of growth and infection conditions, including iron-positive conditions (reported to suppress IsdA expression). The structure has a tail up to 4 μm in length and has a typical orientation parallel to the surface of mammalian cells. It was observed that the detached IsdA-positive structure adhered to the surface of epithelial cells, but lost cell junction localization. Epithelial / bacterial interactions can stimulate the expression of this structure. In addition, we found that IsdA was well conserved between different strains (present in 36 of the 36 strains tested; see below), thus providing protection over a wide population of circulating strains. Found to bring. Since iron uptake is important for virulence, this protein appears to be beneficial for immune attack at the pathological stage of the bacterial life cycle. We have found that this protein is not cytotoxic to human cells (see below). This protein can also be reasonably well adsorbed on aluminum hydroxide (see below), which is useful for stable formulations for delivery to humans. This is useful for providing an immune response and preventing the spread of bacteria by the blood.

0628EsxA and EsxB are small acidic dimer-secreting proteins. We found that EsxA was highly conserved between different strains (existing in 36 of the 36 strains tested; see below), while EsxB was present in 25 of the 36 strains. I found out to do. This protein appears to be beneficial for immune attack at the pathological stage of the bacterial life cycle as it is involved in sustaining infection. We have found that the fusion of EsxA and EsxB (EsxAB) is not cytotoxic to human cells (see below). It can also adsorb well to aluminum hydroxide (see below), which is useful for stable formulations for human delivery. Thus, this antigen is useful for providing an immune response and preventing bacterial spread by the blood.

0629Hla is a pore-forming secretory toxin. This protein is well conserved between different strains (present in 36 of the 36 strains tested; see below), thus providing protection across a large population of circulating strains. Since it is an important virulence factor, it appears to be beneficial for immune attack at the pathological stage of the bacterial life cycle. It is not cytotoxic to human cells (see below). This protein can be reasonably well adsorbed on aluminum hydroxide (see below), which is useful for stable formulations for human delivery. This is useful for providing an immune response and preventing pneumonia.

0630Spa is a surface protein involved in Fc binding. We have found that this protein is well conserved between different strains (present in 36 of the 36 strains tested) and thus provides protection over a large population of circulating strains. Since this is important for virulence, it appears to be beneficial for immune attack at the pathological stage of the bacterial life cycle. The protein can also be reasonably well adsorbed on aluminum hydroxide (see below), which is useful for stable formulations for human delivery. This is useful for providing an immune response and preventing the spread of bacteria by the blood.

0631Sta006 (also known as FhuD2) is a surface protein involved in iron uptake. We found that this protein is well conserved between different strains (present in 36 of the 36 strains tested; see below), thus providing protection over a large population of circulating strains. I found that. We have found that proteins are not cytotoxic to human cells (see below). This protein can also be well adsorbed on aluminum hydroxide (see below), which is useful for stable formulations for delivery to humans. This is useful for providing an immune response and preventing the spread of bacteria by the blood.

0632Sta011 is a surface lipoprotein. We found that this protein is well conserved between different strains (present in 36 of the 36 strains tested; see below), thus providing protection over a large population of circulating strains. I found that. We have found that this protein is not cytotoxic to human cells (see below). The protein can also be reasonably well adsorbed on aluminum hydroxide (see below), which is useful for stable formulations for human delivery. This is useful for providing an immune response and preventing the spread of bacteria by the blood. This protein is Ca⁺⁺Assembled into oligomers in the presence of ions, but Mg⁺⁺It was shown that this is not the case in the presence of ions (see Figure 8). These experiments used 5 μg of recombinant untagged Sta011 at 37 ° C for 25 minutes with increasing CaCl from 0.5 to 50 mM.₂Incubated to a concentration and then analyzed by gel electrophoresis on a clear, non-denatured gel. Ca with a mobility shift (indicating oligomerization) of 2 mM⁺⁺It was clear, especially from&gt; 5 mM. These levels are about 1.2 mM blood Ca⁺⁺Concentration, comparable to serum concentration of about 11 mM and milk concentration of about 32 mM. EDTA reversed the shift.

0633By surface digestion [302] and / or analysis of secretory proteins

0634<chemistry num="8"><img id="000010" he="48" wi="153" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></chemistry>Peptide fragments from, eg, SEQ ID NOs: 228 and 229, were identified as fragments of sta019.

0635Bacterial capsular sugars are useful for providing opsonin immunity. Serotypes 5 and 8 span approximately 85% of clinically isolated strains.

0636(Scope of application of shares) Using a panel of 36 clinically isolated strains, strains belonging to 5 clonal strains representing the majority of CA-MRSA (community-associated methicillin-resistant S. aureus) circulating worldwide. Represented a circulating strain, including. HA-MRSA (nosocomial MRSA) and non-MRSA strains were also included. The entire panel included 9 HA-MRSA strains, 7 CA-MRSA strains, 2 MRSA strains and 18 other strains.

0637Genes encoding IsdA, Hla, EsxA, Sta006, Sta011, Spa and ClfB were present in all 36 strains. The gene for EsxB was absent in 11 of 36 strains and the gene for SdrD was absent in 6 of 36 strains.

0638The encoded IsdA sequence was 95-100% identical across panels and the protein was expressed under iron-restricted conditions during the steady-state growth phase. The coded SdrD array is 30 out of 36 SdrD^+veThe panel members were 95-100% identical. The encoded EsxA sequence was 100% identical across the panels. The coded EsxB array is 25 EsxB^+veThe strains were 95-100% identical. The encoded ClfB sequence was 93-100% identical across panels, and the protein was also found to be highly surface-exposed early in the logarithmic growth phase.

0639Conservation in the encoded amino acid sequence was as follows (% identity):

0640<maths num="1"><img id="000011" he="16" wi="149" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths> A larger panel of 61 strains was screened for the presence of genes encoding Hla and Sta006, as well as their expression. This panel spanned both MRSA and MSSA strains of various geographic origins and of various ST and clonal complex types. Nine of the 61 strains did not express Hla, but all but one expressed Sta006 (data for the 61st strain were not conclusive). Thus, vaccines based on Hla alone do not appear to provide adequate coverage for universal vaccines, but this problem can be overcome by adding Sta006.

0641(Cytotoxicity and cell junction studies) Analysis of possible cytotoxicity in cells by the S. aureus recombinant antigens Hla, Hla-H35L, IsdA, IsdB, sta006, sta011 and EsxAB was performed on HBMEC and A549 cells. The percentage of early and late apoptotic cells was measured by flow cytometry using Annexin V and propidium iodide staining. Endothelial cells were grown in 24-well plates to full confluence. Cells were then incubated with 3 different concentrations of recombinant antigen (10 μg / ml, 1 μg / ml, 0.1 μg / ml) for 24 hours. A combination of TNF-α and cyclohexidine (CHX), which has been reported to induce apoptosis in endothelial cells, was used as a positive control. Incubation with PBS buffer alone was used as a negative control. Analysis was then performed by FACS.

0642Neither antigen induced a cytotoxic effect on HBMEC or A549 cells. In fact, the percentage of viable cell population compared to control cells remained essentially constant until 24 hours of incubation. In contrast, the combination of TNF-α and CHX induced a 25% increase in the number of apoptotic cells.

0643HBMEC was also used as an in vitro model for testing the binding of S. aureus recombinant antigen to human endothelial cells. HBMEC to confluence in a humidified atmosphere at 37 ° C, 10% heat-inactivated fetal bovine serum, 10% NuSerum, 2 mM glutamine, 1 mM pyruvate, 1% non-essential amino acids, 1% MEM vitamins, 100 units / ml penicillin And grown in RPMI 1640 medium supplemented with 100 μg / ml streptomycin. Recombinant antigen binding to cells was tested by indirect immunofluorescence and analyzed by FACS. Cells with positive binding were measured as the net mean intensity of fluorescence relative to the negative control identified as non-specific antibody recognition. The binding experiment was performed at 4 ° C. A mouse polyclonal antibody specific for each of the recombinant antigens was used as the primary antibody, and the binding was detected by the R-phycoerythrin-conjugated goat anti-mouse IgG secondary antibody. As a negative control, HBMEC was incubated with a primary polyclonal antibody detected with a fluorescently labeled secondary antibody, or with only a fluorescently labeled secondary antibody. Binding of known surface-exposed GBS antigen was used as a positive control.

0644Hla and Hla-H35L were the only antigens that could strongly bind to endothelial cells. Hemolytic activity of these two antigens was also tested.

0645Sheep and rabbit fibrin-depleted blood were used and their hemolytic activity was measured by spectroscopic assay. Blood was incubated with 1: 4 serial dilutions of the two proteins at 37 ° C for 30 minutes. Incubation with water, which causes osmotic lysis, and incubation with S. pyogenes protein were used as positive controls, and blood was incubated with PBS + BSA 0.5% as a negative control.

0646Recombinant native Hla exhibited hemolytic activity against rabbit erythrocytes, unlike its H35L mutant morphology. Hemolyticity of the mutant was at least 1/150 lower than that of the wild type. Neither of these proteins had hemolytic activity on sheep blood.

0647Thus, candidates for the S. aureus recombinant vaccine show no cytotoxicity to both the A549 epithelial cell line and the HBMEC endothelial cell line. Importantly, Hla, a secretory toxin known to form pores in the cell membrane of host cells, was able to bind to A549 cells but did not induce cytotoxicity to them. It could also induce hemolysis of rabbit erythrocytes. In contrast, recombinant Hla-H35L, a variant toxin with a single amino acid substitution that is unable to form cytolytic pores, did not induce cell damage in both human cell lines and rabbit erythrocytes. These findings indicate that this variant of Hla morphology can be used more safely in vaccine compositions. None of the other antigens showed the ability to bind to host cells.

0648(Summary formulation) Selected S. aureus protein antigen candidates were formulated individually or as a combination of proteins, with or without capsular polysaccharide conjugate (s), with aluminum hydroxide. The formulation was optimized for pH and volume osmolality.

0649Antigens are EsxA-B, Sta006, Sta011, Hla-H35L, SdrD, IsdA, IsdA_40-184,Sta019,Sta021,Sta073,ClfB_45-552, SdrD_53-592, SasF and IsdB. These are prescribed at 100 μg / ml as the monovalent antigen or at 50 μg / ml in combination, respectively. Capsular sugar conjugates from type 5 or 8 strains are added at 5 μg / ml, 10 μg / ml or 25 μg / ml. Aluminum hydroxide was used at 2 mg / ml with 9 mg / ml NaCl in 10 mM histidine buffer (pH 6.5).

0650All monovalent and combination formulations with or without conjugates could be adjusted for the desired pH and weight osmolality. The formulation had a pH in the range of 6.2 to 7.3 and a weight osmolal concentration in the range of 248 to 360 mOsm / kg. Glycerol had a negative effect on weight osmolality and was excluded from the formulation.

0651All proteins tested in various monovalent and combination formulations are IsdA, IsdA_40-184, Sta019 and Sta073 were well adsorbed on the aluminum hydroxide adjuvant.

0652The individual Sta006, Sta011, EsxA-B and Hla-H35L proteins were completely adsorbed and could be desorbed without altering their pre-adsorption electrophoresis profile.

0653Each antigen in the combination of Sta006, Sta011, EsxA-B and Hla-H35L was completely adsorbed without competition between antigens for the adjuvant. Sta006, Sta011, EsxA-B and IsdA_40-184The antigen in the combination of IsdA behaved in the same manner as the monovalent protein._40-184Except for, it was completely adsorbed. For both combinations, the antigens could be desorbed without altering their pre-adsorption electrophoresis profile.

0654The presence of additional type 5 and / or type 8 conjugates also did not alter the characteristics of antigen adsorption or desorption, for example in the combination of Sta006 + Sta011 + EsxA-B.

0655A short stability study (2 weeks at 4 ° C) was performed to assess the stability of the monovalent formulation and to assess the integrity of the antigen. All tested formulations were stable for their pH and weight osmolality. All antigens remained completely adsorbed on the adjuvant. All antigens maintained their desorption properties. There was no evidence of increased antigen degradation or aggregation after desorption.

0656(Effectiveness test) Individual antigens sta006, sta011, sta012, sta017, sta019, sta021 and sta028, 1.2 × 10⁷The ability of cfu to defend against IV challenges by the Newman strain (type 5) was tested. The results are shown in Figure 1. All antigens reduced the number of bacteria compared to controls and best results were observed using sta006, sta011 and sta019.

0657Additional individual antigens were tested: (i) NW_10; (ii) IsdA_40-184; (iii) Sta002; (iv) Sta003; (v) Sta073; (vi) Sta101; (vii) Sta014; (viii) Hla-PSGS; (ix) SdrD_CnaB.. Increased survival compared to the negative control group was (i) 50%; (ii) 19%; (iii) 37%; (iv) 43%; (v) 25%; (vi) 12 after 15 days of challenge. %; (vii) 25%; (viii) 56%; (ix) 39%.

0658Two hybrid polypeptides were also tested: (i) HlaH35L-EsxAB; (ii) Sta006-EsxAB. The increase in survival after challenge compared to the negative control group was (i) 25%; (ii) 25%.

0659Table 2 summarizes the results obtained with various antigens in the abscess model.

0660In experiment SA-10-a, the efficacy of the antigen combination was tested. Six groups of 12 CD-1 mice were given one of the following combinations supplemented with a negative control (PBS), IsdB or aluminum hydroxide as an adjuvant: (i) EsxAB + Hla-H35L; (ii) Sta006 + Sta011 + EsxAB; (iii) Sta006 + Sta011 + EsxAB + Hla-H35L; or (iv) Sta006 + Sta011 + IsdA_40-184+ EsxAB. Two doses were given on days 0 and 14. On the 24th day, 3x10 on the mouse⁸The cfu Newman strain staphylococci were given and survival in each group was assessed every 24 hours for 2 weeks. The result is shown in figure 2. After 14 days, 25% of the animals in the positive control group survived, but 58% of the animals in groups (iii) and (iv) and 75% in group (i) survived, as well as group (ii). 50% of the animals survived.

0661In Experiment SA-10-b, the same method was used to (i) ClfB._45-552+Hla-H35L+Sta006+EsxAB;(ii)ClfB_45-552+Sta011+Sta006+EsxAB;(iii)ClfB_45-552+IsdA_40-184+ Sta006 + EsxAB; or (iv) SdrD_53-592+IsdA_40-184+ Sta006 + EsxAB was tested. The results are shown in Figure 3. After 14 days, 25% of the animals in the positive control group and group (ii) survived, but 33% of the animals in group (iv), 75% of the animals in group (i), and the animals in group (iii). 83% survived.

0662Mice were immunized using additional combinations. The combination was typically added with aluminum hydroxide as an adjuvant (see above) and administered on days 0 and 14. Immunization was performed on 12 CD1 mice per group. On day 24, mice were challenged with lethal doses of live bacteria and then followed for another 14 days of survival. For comparison, PBS was used as a negative control and IsdB was used as a positive control [2].

0663In Experiment SA-11, (i) type 5 conjugate combined with EsxAB + Sta006 + Sta011; (ii) EsxAB + Sta019 + Sta006 + Sta011; (iii) type 5 conjugate + Hla-H35L + Sta006 + Sta011; ( iv) EsxAB + Hla-H35L + Sta006 + Sta011; or (v) EsxAB + IsdA_40-184+ Sta006 + Sta011 was tested. Fourteen days after the challenge, all negative control animals died, but 42% of the positive control animals survived. Survival results in the study group were as follows: (i) 67%; (ii) 42%; (iii) 75%; (iv) 33%; and (v) 25%.

0664In Experiment SA-12, (i) Hla-H35L + IsdA_40-184+Sta006+Sta011;(ii)Hla-H35L+EsxAB+Sta006+Sta011;(iii)EsxAB+IsdA_40-184+ Sta006 + Sta011; (iv) EsxAB + IsdA + Sta006 + Sta011 were tested. After 14 days of challenge, 8% of negative control animals and 17% of positive control animals survived. Survival results in the study group were as follows: (i) 50%; (ii) 50%; (iii) 25%; (iv) 33%.

0665In Experiment SA-14, (i) EsxAB + Hla-H35L + Sta006 + Sta011; (ii) EsxAB + IsdA_40-184+ Sta006 + Sta011; (iii) Sta006 + Sta011 + Sta019 + EsxAB; (iv) Sta006 + Sta011 + Sta019 + Hla-H35L were tested. 5 × 10⁸After 14 days of challenge with the Newman strain of CFU, 18% of negative control animals and 9% of positive control animals survived. Survival results in the study group were as follows: (i) 58%; (ii) 67%; (iii) 42%; (iv) 83%. Survival numbers over 14 days are shown in Figure 4, indicating that all combinations performed better than the two controls on all days after the challenge.

0666In Experiment SA-17a, (i) EsxAB + Sta006 + Sta011 + serotype 5 conjugate + serotype 8 conjugate; (ii) EsxAB + Sta073 + Sta011 + serotype 5 conjugate + serotype 8 conjugate; (iii) EsxAB + Hla-H35L + Sta011 + Sta073 were tested. Compared to the negative control, the increased survival after 15 days of challenge with the Newman strain was (i) 17%; (ii) 42%; (iii) 34%. The median survival in groups (ii) and (iii) was 15 days of expiration and 12 days in group (i).

0667In further antigen combination experiments, (a) serotype 5 conjugate + serotype 8 conjugate + EsxAB + Sta006 + Sta011; (b) Sta002 + Sta003 + Sta021 + NW-10; (c) EsxAB + HlaH35L + Sta006 + Sta019; and (d) EsxAB + Sta006 + Sta019 were tested. Compared to the negative control, the increased survival after challenge with the Newman strain was (a) 37%; (b) 36%; (c) 13%; and (d) 0%.

0668Survival data from studies SA-10, SA-11, SA-12 and SA-14 were combined to assess the efficacy of the two combinations when compared to PBS or IsdB. "Combo-1" was EsxAB + Hla-H35L + Sta006 + Sta011 (using polypeptides containing SEQ ID NOs: 241, 150, 246 and 247). "Combo-2" is EsxAB + IsdA_40-184It was + Sta006 + Sta011. The median survival time for each group of 48 mice after 14 days was compared. The median survival time of the PBS and IsdB groups was 1 day, whereas the median survival time of the mice in the "Combo-1" and "Combo-2" groups was 14 days. Differences in median survival were compared by t-test. Survival of the "Combo-1" group was statistically superior to that of both the PBS group (p &lt;0.0001) and IsdB group (p &lt;0.0001), and survival of the "Combo-2" group was better than that of the PBS group (p &lt;0.0001). It was statistically superior to both 0.0001) and the IsdB group (p = 0.0049). These data are shown in Figure 5.

0669Figure 6 shows data using Combo-1 and Combo-2 in an abscess model. Mouse kidneys were isolated after the challenge, homogenized and placed on plates. The cfu number indicates the level of abscess formation. FIG. 6 shows data from a single experiment. The numbers below the data indicate log reductions for the PBS group. The reduction is greater in the two combination groups than using IsdB alone, with U-test (one-sided) values of 0.0001 for Combo-1 and 0.0005 for Combo-2. The same effect was observed in the two combination groups in the second experiment, which did not include the IsdB group.

0670In a further experiment, we compared the defenses achieved with Combo-1, IsdB or PBS against challenges with three different strains: Staph-19, FPR3757 (USA300) and Lac (USA300). There were 44 mice per group, and the results were one-sided p-values for survival (where P1 compared Combo-1 to PBS, P2 compared Combo-1 to IsdB, P3, Including (Compare PBS with IsdB), it was as follows (see also Figure 12):

0671<maths num="2"><img id="000012" he="55" wi="152" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths> Further experiments showed that adjuvanted Combo1 reduced post-challenge CFU numbers in the Newman, USA100, CC30 and USA300 strains when compared to immunostimulant alone (aluminum hydroxide) or Immunization with IsdB. Indicated. FIG. 10 shows the CFU values (log / ml) for the four challenge strains. The lowest count of p &lt;0.015 in each case was achieved using Combo1. The area of the abscess was also evaluated, which was also lower in Combo1 immunized mice (eg, Figure 11).

0672Further experiments showed that Combo1 was highly defensive against clinically relevant strains in the sepsis model and always achieved a higher% survival than IsdB. Figure 12 shows that median survival in Combo1 immunized mice (40 per group, 3 experiments) was 15 days of expiration when challenged with Newman, ST-80, FPR3757 or Lac strains and survived. It is shown that the proportion of the mice that were immunized was 75%. In contrast, median survival in IsdB-immunized mice was only 1 day with the Newman and ST-80 challenges, with &lt;65% survival for all 4 challenge strains.

0673(Comparison of Combo1 and its individual polypeptides) Various tests were performed to compare Combo1 to its four individual polypeptides (ie, EsxAB, Hla-H35L, Sta006, Sta011) and IsdB or antigen-free negative controls.

0674The opsonizing activity of sera from immunized animals was tested. Serum was obtained using (i) four individual polypeptides, (ii) all pairs of polypeptides, (iii) all triplets, or (iv) a complete Combo1 combination. Anti-IsdB sera were used for comparison. Pre-immune and negative control sera did not show killing of the Newman strain in this assay. In the first experiment, anti-IsdB sera showed 27% death, sera for each of the four individual polypeptides showed 26-34% death, and all multiple polypeptide combinations showed at least 34. Shows% death, and serum produced with Combo-1 showed 39% death. In the second experiment, Combo-1 sera showed 43% death, while anti-IsdB sera worked slightly better, and all single or multiple polypeptide sera using Combo-1 polypeptide , Showed at least 26% death.

0675In further experiments, we observed the passive defense achieved by transferring antisera from immunized rabbits to mice (20 per group, 8-week-old CD1 mice). Four groups were fed 200 μl of serum from rabbits immunized with one of EsxAB, Hla-H35L, Sta006, Sta011. Group 5 received 50 μl of each serum (200 μl total). The other two groups received serum from IsdB-immunized rabbits or serum from saline-immunized rabbits. After 15 minutes, challenge the mouse intraperitoneally (10)⁸CFU's Newman strain), followed by mortality after 14 days. The results were as follows.

0676<maths num="3"><img id="000013" he="18" wi="149" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths> In a further experiment, the levels of specific antibodies induced in CD1 mice were examined to assess the immunogenicity of the four polypeptides in Combo1. The composition contained either 20 μg of each of the four single polypeptides, or 4 × 10 μg in combination. The composition contained an aluminum hydroxide adjuvant. Serum levels of antigen-specific IgG were determined by the Luminex 4 Plex assay. As shown in FIG. 9, all four polypeptides were highly immunogenic in CD1 mice, both by themselves and in combination. In each case, the titers for the polypeptide were higher when administered in combination than when administered alone (compare the middle pair with the right pair).

0677Further experiments compared the protection achieved with Combo-1 or any of its four individual polypeptides. IsdB is also included for comparison. Percentage of animals (40 animals per group) surviving 15 days after the challenge with the Newman strain, and mean (median) survival over days, included one-sided p-values of survival compared to PBS + adjuvant-negative controls. So, it was as follows.

0678<maths num="4"><img id="000014" he="30" wi="149" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths> A mouse abscess model was used to compare four individual polypeptides with the Combo1 combination. In some experiments, mice were immunized with IsdB for comparison. As the antigen, aluminum hydroxide was added as an adjuvant, and only the adjuvant was used as a negative control. Figure 7 shows the number of bacteria in the kidneys of animals after the challenge with four different strains. The lowest mean counts were observed with the Combo1 combination.

0679Challenge experiments were performed after immunization with (i) four individual polypeptides, (ii) all pairs, (iii) all triples, or (iv) a complete Combo1 combination. Only IsdB or buffer was used for comparison. 5 × 10⁸The results of survival from 24 mice per group after the challenge with the Newman strain of CFU (3 experiments) are shown in Figure 13. The median survival for IsdB was only 2 days. Median survival for individual Combo1 polypeptides ranged from 1 to 6 days. Median survival of pairs of polypeptides was 2-11 days. The median survival of the triplet was 8-15 days. The median survival of the complete Combo1 combination was 15 days of expiration, with 59% of mice surviving at this length (see only 35% using IsdB).

0680It is understood that the invention is described only as an example and that modifications can be made while remaining within the scope and spirit of the invention.

0681<tables num="1-1"><img id="000015" he="180" wi="150" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0682<tables num="1-2"><img id="000016" he="229" wi="150" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0683<tables num="1-3"><img id="000017" he="229" wi="150" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0684<tables num="1-4"><img id="000018" he="214" wi="147" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0685<tables num="2-1"><img id="000019" he="230" wi="145" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0686<tables num="2-2"><img id="000020" he="228" wi="146" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0687<tables num="2-3"><img id="000021" he="228" wi="146" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables>

0688<tables num="2-4"><img id="000022" he="27" wi="155" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></tables> (references)

0689<maths num="5"><img id="000023" he="192" wi="86" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0690<maths num="6"><img id="000024" he="225" wi="142" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0691<maths num="7"><img id="000025" he="227" wi="156" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0692<maths num="8"><img id="000026" he="227" wi="157" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0693<maths num="9"><img id="000027" he="227" wi="153" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0694<maths num="10"><img id="000028" he="224" wi="108" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>

0695<maths num="11"><img id="000029" he="202" wi="154" file="JP2017193574A_D0001.tif" img-format="tif" img-content="drawing" /></maths>