Norovirus vaccine formulations
View Patent ↗The present invention relates to antigenic and vaccine compositions comprising Norovirus antigens and adjuvants, in particular, mixtures of monovalent VLPs and mixtures of multivalent VLPs, and to a process for the production of both monovalent and multivalent VLPs, the VLPs comprising capsid proteins from one or more Norovirus genogroups.
1. A composition comprising at least one Norovirus antigen and at least one adjuvant, wherein the adjuvant is a toll-like receptor (TLR) agonist, and wherein the composition is formulated as a liquid.
2. The composition of claim 1 , wherein the adjuvant is a toll-like receptor 4 (TLR-4) agonist.
3. The composition of claim 2 , wherein the TLR-4 agonist is lipid A, synthetic lipid A, a lipid A mimetic, or a lipid A analog.
4. The composition of claim 2 , wherein the TLR-4 agonist is monophosphoryl lipid A (MPL).
5. The composition of claim 1 , wherein said Norovirus antigen comprises peptides, proteins Norovirus virus-like particles (VLPs), denatured VLPs, capsid monomers, capsid multimers, aggregates, or mixtures thereof.
6. The composition of claim 5 , wherein said Norovirus antigen is selected from the group consisting of Norovirus genogroup I and genogroup II viral strains.
7. The composition of claim 5 , wherein said Norovirus antigen comprises Norovirus VLPs.
8. The composition of claim 7 , wherein said Norovirus VLPs comprise a capsid protein.
9. The composition of claim 8 , wherein said capsid protein is selected from the group consisting of VP1 and VP2.
10. The composition of claim 7 , wherein the VLPs are monovalent VLPs.
11. The composition of claim 7 , wherein the VLPs are multivalent VLPs.
12. The composition of claim 11 , wherein the multivalent VLPs are selected from the group consisting of genogroup I and genogroup II Noroviruses.
13. The composition of claim 7 , wherein the Norovirus VLPs are produced in a recombinant cellular expression system or a baculovirus-infected cellular expression system.
14. The composition of claim 13 , wherein the cellular expression system is selected from the group consisting of yeast, bacterial, insect, and mammalian expression system.
15. The composition of claim 1 , further comprising a second Norovirus antigen.
16. The composition of claim 15 , wherein said first and second Norovirus antigens are monovalent VLPs from different genogroups.
17. The composition of claim 16 , wherein said first Norovirus antigen is a monovalent VLP comprising at least one capsid protein from a genogroup I Norovirus and said second Norovirus antigen is a monovalent VLP comprising at least one capsid protein from a genogroup II Norovirus.
18. The composition of claim 17 , wherein the genogroup II Norovirus is a GII.4 Norovirus.
19. A vaccine formulation comprising the composition of claim 1 .
20. The formulation of claim 19 , wherein the Norovirus antigen is present in a concentration of from about 0.01% (w/w) to about 80% (w/w).
21. The formulation of claim 19 , wherein the dosage of the Norovirus antigen is present in an amount of from about 1 μg to about 100 mg per dose.
22. The formulation of claim 21 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 1 mg per dose.
23. The formulation of claim 21 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 500 μg per dose.
24. The formulation of claim 21 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 150 μg per dose.
25. The composition of claim 1 , wherein the composition is formulated for parenteral administration.
26. The composition of claim 1 , further comprising oil.
27. The composition of claim 1 , further comprising an aluminum salt.
28. The composition of claim 1 , wherein the composition is formulated for intranasal administration.
29. The composition of claim 28 , wherein the formulation is in the form of a nasal spray or nasal drops.
30. The composition of claim 28 , further comprising chitosan.
31. A composition comprising at least one Norovirus antigen and an aluminum salt, wherein the composition is formulated as a liquid.
32. A method of inducing an immune response to Norovirus in a mammal comprising administering to the mammal a composition comprising a Norovirus antigen and at least one adjuvant, wherein said adjuvant is not a bacterial exotoxin, and wherein the Norovirus antigen is from a genogroup I or genogroup II Norovirus.