Flavivirus Vaccines

• US 20090191240A1
• Filed: 12/01/2008
• Published: 07/30/2009
• Est. Priority Date: 01/15/2002
• Status: Abandoned Application

• Current Assignee: Farshad Guirakhoo, Juan Arroyo, Konstantin Pugachev, Thomas P. Monath
• Original Assignee: Farshad Guirakhoo, Juan Arroyo, Konstantin Pugachev, Thomas P. Monath
• Inventors: Arroyo, Juan, Pugachev, Konstantin, Monath, Thomas P., Guirakhoo, Farshad
• Application Number:
  US12/325,864
• Publication Number:
  US 20090191240A1
• Time in Patent Office: Days
• US Class Current: 424/218.1
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2770/24122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2770/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/24162 by genetic engineering
• 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
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides flavivirus vaccines and methods of making and using these vaccines.

Claims

1. a flavivirus comprising a hinge region mutation that reduces viscerotropism of said flavivirus.

2. The flavivirus of claim 1, wherein said flavivirus comprises a yellow fever virus vaccine strain.

3. The flavivirus of claim 1, wherein said flavivirus is a viscerotropic flavivirus selected from the group consisting of Dengue virus, West Nile virus, Wesselsbron virus, Kyasanur Forest Disease virus, and Omsk Hemorrhagic fever virus.

4. The flavivirus of claim 1, wherein said flavivirus is a chimeric flavivirus.

5. The flavivirus of claim 4, wherein said chimeric flavivirus comprises the capsid and non-structural proteins of a first flavivirus virus and the pre-membrane and envelope proteins of a second flavivirus comprising an envelope protein mutation that decreases viscerotropism of said chimeric flavivirus.

6. The flavivirus of claim 5, wherein said second flavivirus is a Japanese encephalitis virus.

7. The flavivirus of claim 5, wherein said second flavivirus is a Dengue virus.

8. The flavivirus of claim 7, wherein said Dengue virus is Dengue-1, Dengue-2, Dengue-3, or Dengue-4 virus.

9. The flavivirus of claim 7, wherein said mutation is in the lysine at Dengue envelope amino acid position 202 or 204.

10. The flavivirus of claim 9, wherein said mutation is a substitution of said lysine.

11. The flavivirus of claim 10, wherein said lysine is substituted with arginine.

12. A vaccine composition comprising the flavivirus of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. A method of inducing an immune response to a flavivirus in a patient, said method comprising administering to said patient the vaccine composition of claim 12.

14. The method of claim 13, wherein said patient does not have, but is at risk of developing, said flavivirus infection.

15. The method of claim 13, wherein said patient has said flavivirus infection.

16. A method of producing a flavivirus vaccine, said method comprising introducing into said flavivirus a mutation that results in decreased viscerotropism.

17. A method of identifying a flavivirus vaccine candidate, said method comprising the steps of:

introducing a mutation into the hinge region of said flavivirus; and

determining whether the flavivirus comprising said hinge region mutation has decreased viscerotropism, as compared with a flavivirus virus lacking the mutation.

18. The method of claim 17, wherein said flavivirus is a yellow fever virus.

19. The method of claim 17, wherein said flavivirus is a chimeric flavivirus.