Norovirus particle for use as an antiviral or vaccine

• US 8,277,819 B2
• Filed: 06/15/2006
• Issued: 10/02/2012
• Est. Priority Date: 06/16/2005
• Status: Expired due to Fees

• Current Assignee: Children's Hospital & Medical Center
• Original Assignee: Children's Hospital & Medical Center
• Inventors: Jiang, Xi, Tan, Ming
• Primary Examiner(s): Blumel, Benjamin P
• Application Number:
  US11/917,862
• Publication Number:
  US 20090280139A1
• Time in Patent Office: 2,301 Days
• Field of Search: None
• US Class Current: 424/216.1
• CPC Class Codes: A61K 2039/5258 Virus-like particles
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2770/16022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/16023 Virus like particles [VLP]
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

Norovirus capsid protein monomers having only the P domain, and not the hinge or S domain, can assemble spontaneously into an icosahedral form herein called the P-particle. Factors affecting the formation and stability of the P-particle, as well as providing methods for diagnosing and treating Norovirus-infected individuals and creating a vaccine for prevention of Norovirus infection are presented.

Claims

1. A composition for inducing an immune response in an individual against Norovirus, the composition comprising a therapeutic amount of a P-particle in a suitable sterile, nontoxic physiological medium, wherein the P-particle comprises Norovirus capsid P domain monomers selected from the group consisting of SEQ ID NO:

2, a P protein, a P protein without a hinge, a P protein with a hinge and a cysteine linked to the end of a P1 subdomain of the P protein, and mixtures thereof.

2. The vaccine of claim 1, wherein the P-particle comprises capsid P domain monomers from the Norovirus strain VA387.

15. The composition according to claim 1, wherein the P-particle has increased receptor binding activity with human histo-blood group antigens as compared to a P dimer particle.

16. The composition according to claim 1, wherein the P-particle comprises a dimer of the P protein.

17. The composition according to claim 2, wherein the P protein without a hinge further comprises a cysteine linked to the end of the P1 subdomain of the P protein.

3. A method of inducing an immune response in an individual against Norovirus, the method comprising the step of orally or parenterally administering to an individual at least one immunologically effective dose of a composition comprising an isolated P-particle, the P-particle comprising a P protein from a Norovirus strain recombinantly expressed or synthesized from a cDNA comprising a fragment of the cDNA sequence of the capsid protein of the Norovirus strain, and a pharmaceutical carrier, wherein the dose is effective in inducing the immune response in the individual.

4. The method of claim 3, wherein the fragment is SEQ ID NO:

2.

5. The method of claim 3, wherein the protein comprises a cysteine linked to the end of a P1 subdomain of the P protein, and wherein the isolated P-particle comprises a plurality of P-Particles which have been purified.

6. The method of claim 5, wherein the cysteine linked to the end of the P1 subdomain of the protein, results in the P-particle being more stable than the original P-particle without the cysteine linkage.

18. The method according to claim 3, wherein the Norovirus strain is VA387.

7. An isolated P-particle comprising capsid P domain monomers from a Norovirus strain.

8. The isolated P-particle of claim 7, wherein the isolated P-particle comprises a plurality of capsid P domain monomers, the capsid P domain monomers selected from the group consisting of P protein without a hinge, and P protein with a hinge and a cysteine linked to the end of a P1 subdomain of the P protein, and mixtures thereof.

9. The isolated P-particles of claim 8, wherein the P protein without a hinge further comprises a cysteine linked to the end of the P1 subdomain of the P protein.

10. The isolated P-particles of claim 9, wherein the a cysteine linked to the end of a P1 subdomain of the P protein, resulst in the P-particles being more stable than the original P-particles without the cysteine modification.

11. The isolated P-particle of claim 7, wherein the Norovirus strain is selected from the group consisting of NV, MOH, and VA 387.

12. The isolated P-particle of claim 7, wherein the Norovirus strain is selected from the group consisting of NV, MOH, Mexico, VA207, VA387, 02-1419, C59, VA115, Hawaii, Snow Mountain, Hillington, Toronto, Leeds, Amsterdam, Idaho Falls, Lordsdale, Grimsby, Southampton, Desert Shield, Birmingham, and White Rivercap.

13. The isolated P-particle of claim 7, wherein the P-particle is a purified recombinant P-particle in the shape of an icosahedron, the icosahedron comprised of 24 monomer units of SEQ ID NO:

2.

14. The isolated P-particle of claim 7, wherein the P-particle comprises capsid P domain monomers from the Norovirus strain VA387.