Nova Patents
CA2840982C

Human respiratory syncytial virus vaccine

Abstract

The present invention relates to RSV vaccines and methods for inducing an immune response to RSV in a subject comprising administering an RSV vaccine.

CA2840982C, drawing sheet 1
Sheet 1 of 25

Term

Projected expiry 6 July 2032.

  1. Priority
  2. Filed
  3. Granted
  4. Today
  5. Projected expiry

41 claims: 19 independent, 22 dependent

  1. 1
    We Claim:1. A vaccine composition comprising (a) a purified, inactivated respiratory syncytial virus (RSV) strain LI9 (RSV-L19) in an amount effective for preventing, treating, or ameliorating a disease caused by a RSV pathogen, and (b) a nanoemulsion adjuvant comprising droplets having an average diameter of greater than 50 nm and less than 1000 nm, that inactivates the RSV virus comprising: i. an aqueous phase;ii. 1% (w/w) to 80% (w/w) of at least one oil;iii. 0.001 % (w/w) to 10% (w/w) of at least one polyoxyethylene nonionic surfactant, a cationic quaternary ammonium compound, or a combination thereof;and iv. 0.1% (w/w) to 50% (w/w) of at least one organic solvent, wherein the organic solvent is an alcohol, wherein the percentages in i-iv are of the nanoemulsion adjuvant (b).
  2. 6
    The vaccine composition of any one of claims 1 to 5 further comprising an additional adjuvant.
  3. 7
    The vaccine composition of any one of claims 1 to 6, wherein the nanoemulsion adjuvant and/or vaccine composition:(a) is not systemically toxic when administered to a subject;(b) produces minimal or no inflammation upon administration;or (c) any combination thereof.
  4. 8
    The vaccine composition of any one of claims 1 to 7, wherein the droplets of the nanoemulsion adjuvant have an average diameter of greater than 50 nm and less than 950 nm, greater than 50 nm and less than 900 nm, greater than 50 nm and less than 850 nm, greater than 50 nm and less than 800 nm, greater than 50 nm and less than 750 nm, greater than 50 nm and less than 700 nm, greater than 50 nm and less than 650 nm, greater than 50 nm and less than 600 nm, greater than 50 nm and less than 550 nm, greater than 50 nm and less than 500 nm, greater than 50 nm and less than 450 nm, greater than 50 nm and less than 400 nm, greater than 50 nm and less than 350 nm, greater than 50 nm and less than 300 nm, greater than 50 nm and less than 250 nm, greater than 50 nm and less than 200 nm, greater than 50 nm and less than 150 nm, greater than 50 nm and less than 100 nm, greater than 70 nm and less than 1000 nm, greater than 125 nm and less than 1000 nm, or greater than 125 nm and less than 600 nm.
  5. 9
    The vaccine composition of any one of claims 1 to 8, wherein administration of the vaccine composition to a subject results in seroconversion of the subject after a single administration of the vaccine composition.
  6. 12
    The vaccine composition of any one of claims 1 to 11, wherein the RSV-L19 comprises a viral genome of RSV L19 comprising at least one attenuating mutation.
  7. 13
    The vaccine composition of any one of claims 1 to 12, further comprising at least one additional pharmaceutically acceptable carrier or excipient.
  8. 14
    The vaccine composition of any one of claims 1 to 13, wherein the alcohol is:(a) a C1 -C12 alcohol, diol, triol, or combinations thereof;(b) a nonpolar solvent, a polar solvent, a protic solvent, an aprotic solvent, semisynthetic derivatives thereof, or combinations thereof;(c) perfumers or sorbitol;or (d) any combination of (a) to (c).
  9. 15
    The vaccine composition of any one of claims 1 to 14, wherein the oil is animal oil, vegetable oil, synthetic oil, hydrocarbon oils, silicone oils, or semi-synthetic derivatives thereof.
  10. 16
    The vaccine composition of any one of claims 1 to 15, wherein:(a) the composition further comprises polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan monooleate, semi-synthetic derivatives thereof, or mixtures thereof;or (b) the cationic quaternary ammonium compound is an alkyl trimethyl ammonium chloride compound, a dialkyl dimethyl ammonium chloride compound, Benzalkonium chloride, Benzyldimethylhexadecylammonium chloride, Benzyldimethyltetradecylammonium chloride, Benzyldodecyldimethylammonium bromide, Benzyltrimethylammonium tetrachloroiodate, Date Reçue/Date Received 2021-02-09 Cetylpyridinium chloride, Dimethyldioctadecylammonium bromide, Dodecylethyldimethylammonium bromide, Dodecyltrimethylammonium bromide. Ethylhexadecyldimethylammonium bromide, Girard's reagent T, Hexadecyltrimethylammonium bromide, N,N’,N'-Polyoxyethylene(10)-N-tallow-l.,3-diaminopropane, Thonzonium bromide, Trimethyl(tetradecyl)ammonium bromide, l,3,5-Triazine-l,3,5(2H,4H,6H)-triethanol, 1Decanaminium, N-decyl-N, N-dimethyl-, chloride. Didecyl dimethyl ammonium chloride, 2-(2(p-(Diisobutyl)cresosxy)ethoxy)ethyl dimethyl benzyl ammonium chloride, 2-(2-(p(Diisobutyl)phenoxy)ethoxy)ethyl dimethyl benzyl ammonium chloride, Alkyl 1 or 3 benzyl-1(2-hydroxethyl)-2-imidazolinium chloride, Alkyl bis(2-hydroxyethyl) benzyl ammonium chloride, Alkyl demethyl benzyl ammonium chloride, Alkyl(100% Cl2) dimethyl 3,4dichlorobenzyl ammonium chloride, Alkyl(50% C14,40% C12,10% C16) dimethyl 3,4dichlorobenzyl ammonium chloride, Alkyl(55% C14,23% C12,20% C16) dimethyl 3,4dichlorobenzyl ammonium chloride, Alkyl dimethyl benzyl ammonium chloride, Alkyl(100% Cl4) dimethyl benzyl ammonium chloride, Alkyl(100% Cl6) dimethyl benzyl ammonium chloride, Alkyl(41% Cl4,28% Cl2) dimethyl benzyl ammonium chloride, Alkyl(47% Cl2,18% Cl4) dimethyl benzyl ammonium chloride, Alkyl(55% Cl6,20% Cl4) dimethyl benzyl ammonium chloride, Alkyl(58% C14,28% C16) dimethyl benzyl ammonium chloride, Alkyl(60% C14,25% C12) dimethyl benzyl ammonium chloride, Alkyl(61 % Cl 1,23% C14) dimethyl benzyl ammonium chloride, Alkyl(61% Cl2,23% Cl4) dimethyl benzyl ammonium chloride, Alkyl(65% Cl2,25% C14) dimethyl benzyl ammonium chloride, Alkyl(67% Cl2,24% Cl4) dimethyl benzyl ammonium chloride, Alkyl(67% C12,25% Cl4) dimethyl benzyl ammonium chloride, Alkyl(90% C14,5% C12) dimethyl benzyl ammonium chloride, Alkyl(93% C14,4% C12) dimethyl benzyl ammonium chloride, Alkyl(95% C16,5% C18) dimethyl benzyl ammonium chloride. Alkyl didecyl dimethyl ammonium chloride, Alkyl(C1216) dimethyl benzyl ammonium chloride, Alkyl(C12-l 8) dimethyl benzyl ammonium chloride, dialkyl dimethyl benzyl ammonium chloride, Alkyl dimethyl dimethybenzyl ammonium chloride, Alkyl(90% C14,5% C16,5% C12) dimethyl ethyl ammonium bromide. Alkyl dimethyl ethyl ammonium bromide and Alkenyl dimethyl ethyl ammonium bromide, Alkyl dimethyl ethylbenzyl ammonium chloride, Alkyl(60% C14) dimethyl ethylbenzyl ammonium chloride, Alkyl(50% Cl2,30% C14,17% Cl6,3% Cl8) dimethyl isopropylbenzyl ammonium chloride, Date Reçue/Date Received 2021-02-09 Alkyl(58% C18,40% C16,1% C14,1% C12) trimethyl ammonium chloride, Alkyl(90% C18, 10% Cl6) trimethyl ammonium chloride, Alkyl(C12-18)dimethyl(ethylbenzyl) ammonium chloride, Di-(C8-10)-alkyl dimethyl ammonium chlorides. Dialkyl dimethyl ammonium chloride, Dialkyl methyl benzyl ammonium chloride, Didecyl dimethyl ammonium chloride, Diisodecyl dimethyl ammonium chloride. Dioctyl dimethyl ammonium chloride. Dodecyl bis(2hydroxyethyl) octyl hydrogen ammonium chloride, Dodecyl dimethyl benzyl ammonium chloride, Dodecylcarbamoyl methyl dinethyl benzyl ammonium chloride. Heptadecyl hydroxyethylimidazolinium chloride, Hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine, Myristalkonium chloride and Quat RNIUM 14, N,N-Dimethyl-2-hydroxypropylammonium chloride polymer, n-Tetradecyl dimethyl benzyl ammonium chloride monohydrate, Octyl decyl dimethyl ammonium chloride, Octyl dodecyl dimethyl ammonium chloride, Octyphenoxyethoxyethyl dimethyl benzyl ammonium chloride, Oxydiethylenebis(alkyl dimethyl ammonium chloride), Trimethoxysily propyl dimethyl octadecyl ammonium chloride, Trimethoxysilyl quats, Trimethyl dodecylbenzyl ammonium chloride, semi-synthetic derivatives thereof, or combinations thereof.
  11. 17
    The vaccine composition of any one of claims 1 to 16, wherein the nanoemulsion adjuvant further comprises at least one cationic surfactant.
  12. 25
    The vaccine composition of any one of claims 17 to 24, wherein the nanoemulsion adjuvant further comprises at least one non-cationic surfactant.
  13. 29
    The vaccine composition of any one of claims 26-28, wherein the nonionic surfactant is polysorbate 20, polysorbate 80, poloxamer 188, poloxamer 407, or a combination thereof.
  14. 30
    The vaccine composition of any one of claims 26-29, wherein the nonionic surfactant is polysorbate 20, polysorbate 80, poloxamer 188, poloxamer 407, and wherein the nonionic Date Reçue/Date Received 2021-02-09 surfactant is present in a concentration of 0.01% (w/w) to 5.0 % (w/w), or at 0.1% (w/w) to 3% (w/w), of the nanoemulsion adjuvant.
  15. 31
    The vaccine composition of any one of claims 1 to 30, further comprising chitosan.
  16. 32
    The vaccine composition of any one of claims 1 to 31, further comprising glucan.
  17. 33
    The vaccine composition of any one of claims 1 to 32, wherein die aqueous phase is present in Phosphate Buffered Saline (PBS).
  18. 34
    Use of the vaccine composition according to any one of claims 1 to 33 for the manufacture of a medicament, for inducing an enhanced immunity against disease caused by human respiratory syncytial virus in a subject in need thereof.
  19. 37
    The use of any one of claims 34 to 36, wherein the medicament is formulated for intranasal administration.
  20. 38
    Use of the vaccine composition according to any one of claims 1 to 33 for inducing an enhanced immunity against disease caused by human respiratory syncytial virus in a subject in need thereof.
  21. 41
    The use of any one of claims 38 to 40, wherein the vaccine composition is formulated for intranasal administration.
Independent claims21