Chimeric dengue virus e glycoproteins comprising mutant domain i and domain ii hinge regions

Abstract

The present invention provides compositions and methods of use comprising a chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone, which comprises amino acid substitutions that introduce a dengue virus E glycoprotein domain I and domain II hinge region from a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone.

1 . (canceled) 
     
     
         2 . A chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone from dengue virus serotype 2 that comprises the following amino acid substitutions that introduce an epitope that is recognized by an antibody that is reactive with a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone; wherein the amino acid residue numbering is based on the amino acid sequence of SEQ ID NO:20:
 Q52E, P53V, T55L, K58T, N124K, M1251, E126T, K128N, V129L, Q200K, E202K, N203K, A205T, R210K, L221T, P222A, Q271D, M272S, S273G, S274D, L277H, L278M, and T280A.   
     
     
         3 . A flavivirus particle or virus like particle (VLP) comprising the E glycoprotein of  claim 2 . 
     
     
         4 . An isolated nucleic acid molecule encoding the E glycoprotein of  claim 2 . 
     
     
         5 . An isolated nucleic acid molecule encoding the flavivirus particle or VLP of  claim 3 . 
     
     
         6 . A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 2  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein. 
     
     
         7 . A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the flavivirus particle or VLP of  claim 3 . 
     
     
         8 . A method of treating and/or preventing a dengue virus infection in a subject in need thereof, the method comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 2  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein. 
     
     
         9 . A method of protecting a subject from the effects of dengue virus infection, the method comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 2  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein. 
     
     
         10 . A chimeric dengue virus E glycoprotein comprising a dengue virus E glycoprotein backbone from dengue virus serotype 3 that comprises the following amino acid substitutions that introduce an epitope that is recognized by an antibody that is reactive with a dengue virus serotype that is different from the dengue virus serotype of the dengue virus E glycoprotein backbone; wherein the amino acid residue numbering is based on the amino acid sequence of SEQ ID NO:17:
 N270T, G273T, and S275T.   
     
     
         11 . A flavivirus particle or virus like particle (VLP) comprising the E glycoprotein of  claim 10 . 
     
     
         12 . An isolated nucleic acid molecule encoding the E glycoprotein of  claim 10 . 
     
     
         13 . An isolated nucleic acid molecule encoding the flavivirus particle or VLP of  claim 11 . 
     
     
         14 . A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 10  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein. 
     
     
         15 . A method of producing an immune response to a dengue virus in a subject, comprising administering to the subject an effective amount of the flavivirus particle or VLP of  claim 11 . 
     
     
         16 . A method of treating and/or preventing a dengue virus infection in a subject in need thereof, the method comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 10  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein. 
     
     
         17 . A method of protecting a subject from the effects of dengue virus infection, the method comprising administering to the subject an effective amount of the chimeric dengue virus E glycoprotein of  claim 10  and/or an isolated nucleic acid molecule expressing said chimeric dengue virus E glycoprotein.