Norovirus vaccine formulations

• US 7,955,603 B2
• Filed: 09/28/2007
• Issued: 06/07/2011
• Est. Priority Date: 09/29/2006
• Status: Active Grant

• Current Assignee: Montana Inc.
• Original Assignee: LigoCyte Pharmaceuticals, Inc. (Takeda Pharmaceutical Company Limited)
• Inventors: Richardson, Charles, Tino, William T., Foubert, Thomas R., Vedvick, Thomas S.
• Primary Examiner(s): LI, BAO Q
• Application Number:
  US12/093,921
• Publication Number:
  US 20080299152A1
• Time in Patent Office: 1,348 Days
• Field of Search: 424/93.1
• US Class Current: 424/204.1
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/543 intranasal
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/125 Picornaviridae, e.g. calicivirus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/10 from RNA viruses
• CPC Class Codes: C12N 2770/16023 Virus like particles [VLP]
• CPC Class Codes: C12N 2770/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

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.

Claims

1. An immunogenic composition comprising at least one Norovirus antigen, chitosan, sucrose, and at least one adjuvant, wherein said antigen comprises Norovirus virus-like particles (VLPs) and the adjuvant is not a bacterial exotoxin, and wherein the composition is formulated as a stable dry powder such that the percent aggregation of VLPs remains relatively constant or decreases when measured over a twelve month period.

2. The composition of claim 1, wherein said Norovirus antigen is selected from the group consisting of Norovirus genogroup I and genogroup II viral strains.

3. The composition of claim 1, wherein said Norovirus VLPs comprise a capsid protein.

4. The composition of claim 3, wherein said capsid protein is VP1 and/or VP2.

5. The composition of claim 1, wherein the VLPs are monovalent VLPs.

6. The composition of claim 1, wherein the VLPs are multivalent VLPs.

7. The composition of claim 6, wherein the multivalent VLPs are selected from the group consisting of genogroup I and genogroup II Noroviruses.

8. The composition of claim 1, wherein the Norovirus VLPs are produced in a recombinant cellular expression system or a baculovirus-infected cellular expression system.

9. The composition of claim 8, wherein the cellular expression system is selected from the group consisting of yeast, bacterial, insect, and mammalian expression system.

10. The composition of claim 1, further comprising a second Norovirus antigen.

11. The composition of claim 10, wherein said first and second Norovirus antigens are monovalent VLPs from different genogroups.

12. The composition of claim 1, wherein the adjuvant is selected from the group consisting of toll-like receptor (TLR) agonists, monophosphoryl lipid A (MPL), synthetic lipid A, lipid A mimetics or analogs, aluminum salts, cytokines, saponins, muramyl dipeptide (MDP) derivatives, CpG oligos, lipopolysaccharide (LPS) of gram-negative bacteria, polyphosphazenes, emulsions, virosomes, cochleates, poly(lactide-co-glycolides) (PLG) microparticles, poloxamer particles, microparticles, and liposomes.

13. The composition of claim 12, wherein the adjuvant is a toll-like receptor (TLR) agonist.

14. The composition of claim 12, wherein the adjuvant is MPL.

15. The composition of claim 1, wherein the composition has an average particle size from about 10 to 500 micrometers in diameter.

16. The composition of claim 1 in combination with one or more devices for administering one or more doses of said composition.

17. The composition of claim 16, wherein said one or more doses are unit doses.

18. The composition of claim 16, wherein the device is a single-use nasal administration device.

19. The composition of claim 16, wherein said composition is stored in said device.

20. The composition of claim 1, wherein said composition is administered to a subject by a mucosal route.

21. The composition of claim 20, wherein the mucosal route of administration is intranasal, oral, or vaginal.

22. The composition of claim 20, wherein the composition is administered to the nasal mucosa by rapid deposition within the nasal passage from a device of the formulation held close or inserted into the nasal passageway.

23. The composition of claim 22, wherein the composition is administered to one or both nostrils.

24. The composition of claim 1, wherein the Norovirus antigen is present in a concentration of from about 0.01% (w/w) to about 80% (w/w).

25. The composition of claim 1, wherein the dosage of the Norovirus antigen is present in an amount of from about 1 μ

g to about 100 mg per dose.

26. The composition of claim 25, wherein the dosage of the Norovirus antigen is from about 1 μ

g to about 1 mg per dose.

27. The composition of claim 25, wherein the dosage of the Norovirus antigen is from about 1 μ

g to about 500 μ

g per dose.

28. The composition of claim 25, wherein the dosage of the Norovirus antigen is from about 1 μ

g to about 100 μ

g per dose.

29. A method of generating antibodies to Norovirus antigens, comprising administering to a subject the composition of claim 1.

30. A method of inducing an immune response in a subject experiencing a Norovirus infection, comprising administering to the subject the composition of claim 1, wherein said immune response is therapeutic.

31. The composition of claim 5, wherein the monovalent VLPs comprise at least one capsid protein from a genogroup II Norovirus.

32. The composition of claim 31, wherein the genogroup II Norovirus is a GII.4 Norovirus.

33. The composition of claim 1, wherein the composition is reconstituted with diluent to form a liquid formulation.

34. The formulation of claim 33, wherein said formulation is designed to be administered to a subject by a route selected from the group consisting of mucosal, intranasal, sublingual, oral, rectal, vaginal, intramuscular, intravenous, subcutaneous, intradermal, subdermal, and transdermal routes of administration.

35. The formulation of claim 34, wherein the route of administration is intramuscular.

36. The formulation of claim 33, wherein the formulation is in the form of a nasal spray or nasal drops.

37. The composition of claim 1, wherein said composition elicits a Norovirus-specific immune response when administered to a mammal.