Flavivirus vaccines

Abstract

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

What is claimed is: 
     
         1 - 21 . (canceled) 
     
     
         22 . A chimeric flavivirus comprising sequences encoding capsid and non-structural proteins of a first flavivirus and pre-membrane and envelope proteins of a dengue virus selected from a dengue-1 virus, a dengue-2 virus, a dengue-3 virus, and a dengue-4 virus, wherein the dengue virus envelope protein has a substitution of the amino acid at position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine. 
     
     
         23 . The chimeric flavivirus of  claim 22 , wherein the dengue virus is a dengue-1 virus. 
     
     
         24 . The chimeric flavivirus of  claim 22 , wherein the dengue virus is a dengue-2 virus. 
     
     
         25 . The chimeric flavivirus of  claim 22 , wherein the dengue virus is a dengue-3 virus. 
     
     
         26 . The chimeric flavivirus of  claim 22 , wherein the dengue virus is a dengue-4 virus. 
     
     
         27 . The chimeric flavivirus of  claim 22 , wherein the first flavivirus is a yellow fever virus. 
     
     
         28 . The chimeric flavivirus of  claim 27 , wherein the yellow fever virus is a yellow fever virus vaccine strain. 
     
     
         29 . The chimeric flavivirus of  claim 28 , wherein the yellow fever virus vaccine strain is YF17D. 
     
     
         30 . An immunogenic composition comprising the chimeric flavivirus of  claim 22  and a pharmaceutically acceptable carrier or diluent. 
     
     
         31 . The immunogenic composition of  claim 30 , further comprising three additional chimeric flaviviruses that each comprise sequences encoding capsid and non-structural proteins of a first flavivirus and pre-membrane and envelope proteins of one of dengue-1, dengue-2, dengue-3, and dengue-4 viruses, wherein the dengue virus sequences of each the three additional chimeric flaviviruses are of dengue serotypes that are different from one another and different from that of the composition of  claim 30 . 
     
     
         32 . The immunogenic composition of  claim 31 , wherein the dengue virus envelope protein of one or more of the three additional chimeras has a substitution of the amino acid at position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine. 
     
     
         33 . A method of inducing an immune response to a flavivirus in a subject, the method comprising administering to the subject a chimeric flavivirus comprising sequences encoding capsid and non-structural proteins of a first flavivirus and pre-membrane and envelope proteins of a dengue virus selected from a dengue-1 virus, a dengue-2 virus, a dengue-3 virus, and a dengue-4 virus, wherein the dengue virus envelope protein has a substitution of the amino acid at position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine. 
     
     
         34 . The method of  claim 33 , wherein the dengue virus is a dengue-1 virus. 
     
     
         35 . The method of  claim 33 , wherein the dengue virus is a dengue-2 virus. 
     
     
         36 . The method of  claim 33 , wherein the dengue virus is a dengue-3 virus. 
     
     
         37 . The method of  claim 33 , wherein the dengue virus is a dengue-4 virus. 
     
     
         38 . The method of  claim 33 , wherein the first flavivirus is a yellow fever virus. 
     
     
         39 . The method of  claim 33 , further comprising administering to the subject three additional chimeric flaviviruses that each comprise sequences encoding capsid and non-structural proteins of a first flavivirus and pre-membrane and envelope proteins of one of dengue-1, dengue-2, dengue-3, and dengue-4 viruses, wherein the dengue virus sequences of each the three additional chimeric flaviviruses are of dengue serotypes that are different from one another and different from that of the method of  claim 33 . 
     
     
         40 . The method of  claim 39 , wherein the dengue virus envelope protein of one or more of the three additional chimeras has a substitution of the amino acid at position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine. 
     
     
         41 . The method of  claim 39 , wherein the chimeric flaviviruses administered to the subject are comprised within an immunogenic composition, prior to administration. 
     
     
         42 . The method of  claim 33 , wherein the flavivirus to which an immune response is sought is a dengue virus. 
     
     
         43 . The method of  claim 33 , wherein the subject does not have, but is at risk of developing, a flavivirus infection. 
     
     
         44 . The method of  claim 43 , wherein the flavivirus infection is a dengue virus infection. 
     
     
         45 . The method of  claim 33 , wherein the subject has a flavivirus infection. 
     
     
         46 . The method of  claim 45 , wherein the flavivirus infection is a dengue virus infection.