Parenteral norovirus vaccine formulations
The present invention relates to single dose parenteral vaccine compositions comprising mixtures of monovalent Norovirus virus-like particles. Methods of conferring protective immunity against Norovirus infections in a human subject by administering such compositions are also disclosed.
1. A method of eliciting protective immunity against Norovirus in a human comprising administering parenterally to the human no more than a single dose of a vaccine composition, said composition comprising
(i) genogroup I Norovirus virus-like particles (VLPs), wherein said genogroup I Norovirus VLPs comprise a capsid protein derived from a genogroup I viral strain, or
(ii) genogroup II Norovirus VLPs, wherein said genogroup II Norovirus VLPs comprise a capsid protein derived from a genogroup II viral strain,
wherein said composition induces at least a three-fold increase in Norovirus-specific serum antibody titer as compared to the titer in the human prior to administration of the composition, and
wherein the composition comprises about 5 μg to about 150 μg of said genogroup I or genogroup II Norovirus VLPs.
2. The method of claim 1 , wherein the composition comprises about 5 μg to about 50 μg of said genogroup I Norovirus VLPs.
3. The method of claim 1 , wherein the composition comprises about 15 μg of said genogroup I Norovirus VLPs.
4. The method of claim 1 , wherein the composition comprises about 25 μg to about 150 μg of said genogroup II Norovirus VLPs.
5. The method of claim 1 , wherein the composition comprises about 50 μg of said genogroup II Norovirus VLPs.
6. The method of claim 1 , wherein the composition induces at least a six-fold increase in Norovirus-specific serum antibody titer as compared to the titer in the human prior to administration of the composition.
7. The method of claim 1 , wherein said Norovirus VLPs are monovalent VLPs or multivalent VLPs.
8. The method of claim 1 , wherein the composition comprises said genogroup I Norovirus VLPs, and wherein said genogroup I Norovirus VLPs are Norwalk virus VLPs.
9. The method of claim 1 , wherein the composition comprises said genogroup II Norovirus VLPs, and wherein said genogroup II Norovirus VLPs are VLPs generated from expression of a consensus sequence of genogroup II Norovirus.
10. The method of claim 1 , wherein the composition further comprises at least one adjuvant.
11. The method of claim 10 , wherein said at least one adjuvant is a toll-like receptor agonist.
12. The method of claim 10 , wherein the adjuvant is selected from monophosphoryl lipid A and aluminum hydroxide.
13. The method of claim 1 , wherein said composition further comprises a buffer.
14. The method of claim 13 , wherein said buffer is selected from the group consisting of L-histidine, imidazole, succinic acid, tris, and citric acid.
15. The method of claim 1 , wherein the vaccine composition is administered to the human by an intravenous, subcutaneous, intradermal, or intramuscular route of administration.
16. The method of claim 15 , wherein the vaccine composition is administered to the human by an intramuscular route of administration.
17. The method of claim 1 , wherein the vaccine composition is formulated as a liquid.
18. The method of claim 1 , wherein the increase in Norovirus-specific antibody titer is induced within seven days of administration of the single dose of the composition.
19. The method of claim 1 , wherein said vaccine composition confers protection from one or more symptoms of Norovirus infection.
20. The method of claim 10 , wherein said at least one adjuvant is an aluminum hydroxide.
21. The method of claim 1 , wherein the composition comprises said genogroup II Norovirus VLPs, and wherein said genogroup II Norovirus VLPs comprise a capsid protein having a sequence of SEQ ID NO: 1.