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