Flavivirus Vaccines

Abstract

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.