Norovirus vaccine formulations
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 a first monovalent virus like particle (VLP) derived from a genogroup I Norovirus and a second monovalent VLP derived from a genogroup II Norovirus and at least one adjuvant, wherein the adjuvant is monophosphoryl lipid A (MPL) and/or an aluminum salt, and wherein the composition is formulated as a liquid.
2. The composition of claim 1 , wherein said Norovirus VLPs comprise a capsid protein.
3. The composition of claim 2 , wherein said capsid protein is selected from the group consisting of VP1 and VP2.
4. The composition of claim 1 , wherein the Norovirus VLPs are produced in a recombinant cellular expression system or a baculovirus-infected cellular expression system.
5. The composition of claim 4 , wherein the cellular expression system is selected from the group consisting of yeast, bacterial, insect, and mammalian expression system.
6. The composition of claim 1 , wherein the genogroup I Norovirus is a GI.1 Norovirus.
7. The composition of claim 1 , wherein the genogroup II Norovirus is a GII.4 Norovirus.
8. The composition of claim 6 , wherein the genogroup II Norovirus is a GII.4 Norovirus.
9. A vaccine formulation comprising the composition of claim 1 .
10. The formulation of claim 9 , wherein the Norovirus VLPs are present in a concentration of from about 0.01% (w/w) to about 80% (w/w).
11. The formulation of claim 10 , wherein the dosage of the Norovirus antigen is present in an amount of from about 1 μg to about 100 mg per dose.
12. The formulation of claim 11 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 1 mg per dose.
13. The formulation of claim 12 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 500 μg per dose.
14. The formulation of claim 13 , wherein the dosage of the Norovirus antigen is from about 1 μg to about 150 μg per dose.
15. The composition of claim 1 , wherein the composition is formulated for parenteral administration.
16. The composition of claim 1 , further comprising oil.
17. The composition of claim 1 , wherein the composition is formulated for intranasal administration.
18. The composition of claim 17 , wherein the formulation is in the form of a nasal spray or nasal drops.
19. The composition of claim 17 , further comprising chitosan.
20. A method of inducing an immune response in a subject, comprising administering to the subject the composition of claim 1 .
21. A method of inducing an immune response in a subject, comprising administering to the subject the vaccine formulation of claim 9 .
22. The composition of claim 1 comprising MPL and alum.
23. A composition comprising a VLP derived from a GI.1 Norovirus, a VLP derived from a GII.4 Norovirus, MPL and alum, wherein the composition is formulated as a liquid.