Flavivirus Vaccine

Abstract

Replicon virus-like particles can be used as flavivirus vaccines.

The invention is claimed as follows: 
     
         1 . A non-replicating flavivirus particle comprising a recombinant replicon that expresses at least one immunologic determinant of a flavivirus envelope protein. 
     
     
         2 . The particle of  claim 1 , wherein said flavivirus particle comprises a dengue virus. 
     
     
         3 . The particle of  claim 1 , wherein said flavivirus particle comprises a West Nile virus. 
     
     
         4 . The particle of  claim 1 , wherein said flavivirus particle comprises a Japanese encephalitis virus. 
     
     
         5 . The particle of  claim 1 , wherein said flavivirus particle comprises a yellow fever virus. 
     
     
         6 . The particle of  claim 1 , wherein said replicon does not express a capsid protein. 
     
     
         7 . The particle of  claim 1 , wherein said replicon expresses at least one immunologic determinant of a premembrane or a membrane protein of said envelope protein. 
     
     
         8 . A pharmaceutical composition comprising the particle of  claim 1  and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         9 . A method of making the particle of  claim 1 , comprising transforming a host cell with said replicon, then transforming said host cell with a replicon that expresses genes that complement said replicon of  claim 1  and isolating particles produced by said host cell. 
     
     
         10 . The method of  claim 9 , wherein said complementing replicon comprises Sindbis virus C, prM and/or E open reading frames. 
     
     
         11 . A method of making the particle of  claim 1 , comprising transforming a host cell with said replicon, wherein said replicon does not express a gene product essential for making an infectious virus particle, wherein said host cell expresses said gene product essential for making an infectious gene particle, and isolating particles produced by said host cell. 
     
     
         12 . The method of  claim 11 , wherein said host cell expresses a C protein. 
     
     
         13 . The method of  claim 12 , wherein expression of said C protein is induced when said host cell is transformed with said replicon. 
     
     
         14 . A transformed cell that expresses said flavivirus envelope protein of  claim 1 . 
     
     
         15 . The transformed cell of  claim 14 , further comprising a flavivirus replicon that does not express a C protein or expresses a C protein that cannot comprise a capsid of an infectious virus particle.