Gene expression vaccine

Abstract

An effective prophylactic mucosal gene expression vaccine (GXV), made up of a cocktail of at least 4 different plasmid DNAs encoding corresponding RSV antigens, coacervated with chitosan to formulate nanospheres. In a murine model of RSV infection, intranasal administration with GXV results in significant induction of RSV-specific antibodies, nasal IgA antibodies, cytotoxic T lymphocytes, and IFN-γ production in the lung and splenocytes. A single dose of GXV induces a drastic reduction of viral titers.

1 . An immunogenic composition for conferring protection in a host against disease caused by respiratory syncytial virus (RSV), comprising: 
 an F RSV antigen;    a G RSV antigen; and    at least one of M, M2, SH, NS1, NS2, N, or P RSV antigen.    
   
   
       2 . The immunogenic composition of  claim 1 , wherein said composition is a mucosal vaccine.  
   
   
       3 . An immunogenic composition for conferring protection in a host against disease caused by respiratory syncytial virus (RSV) comprising: 
 an M2 RSV antigen; and    at least one of F, G, M, SH, NS1, NS2, N, or P RSV antigen.    
   
   
       4 . The immunogenic composition of  claim 3 , wherein said composition is a mucosal vaccine.  
   
   
       5 . An immunogenic composition for conferring protection in a host against disease caused by respiratory syncytial virus (RSV) comprising: 
 an F RSV antigen;    a G RSV antigen; an M2 RSV antigen; and    at least one of M, SH, NS1, NS2, N, or P RSV antigen.    
   
   
       6 . The immunogenic composition of  claim 5 , wherein said composition is a mucosal vaccine.  
   
   
       7 . A gene expression vaccine for conferring protection in a host against disease caused by respiratory synctial virus (RSV) comprising: 
 a plasmid DNA cocktail comprising a combination of at least two RSV antigens selected from the group consisting of F, G, M, M2, SH, NS1, NS2, N, and P; wherein said plasmid DNA cocktail is coacervated with chitosan to form nanospheres.    
   
   
       8 . The gene expression vaccine of  claim 7 , wherein administration does not alter airway hyperresponsiveness.  
   
   
       9 . The gene expression vaccine of  claim 7 , wherein said vaccine is a mucosal vaccine.  
   
   
       10 . The gene expression vaccine of  claim 9 , wherein said mucosal vaccine is conducive to oral administration.  
   
   
       11 . The gene expression vaccine of  claim 9 , wherein said mucosal vaccine is conducive to intranasal administration.  
   
   
       12 . The gene expression vaccine of  claim 7 , wherein administration of said vaccine induces IFN-γ expression.  
   
   
       13 . A method of immunizing a host against disease caused by infection with respiratory syncytial virus (RSV), comprising: 
 administering to said host an immunoeffective amount of a composition comprising:    a plasmid DNA cocktail comprising a combination of at least two RSV antigens selected from the group consisting of F, G, M, M2, SH, NS1, NS2, N, and P; wherein said plasmid DNA cocktail is coacervated with chitosan to form nanospheres.    
   
   
       14 . The method of  claim 13 , wherein said administering is oral or intranasal.  
   
   
       15 . The method of  claim 13 , wherein said administering does not induce airway hyperreactivity.  
   
   
       16 . The method of  claim 13 , wherein said immunoeffective amount is administered in a single dose.  
   
   
       17 . The method of  claim 13 , wherein said immunoeffective amount is about 1 mg/kg host weight.  
   
   
       18 . A method of making a gene expression vaccine comprising: cloning cDNA for at least two respiratory syncytial virus antigens in a pVAX plasmid to form a plasmid DNA cocktail; and coacervating the plasmid DNA cocktail with chitosan.  
   
   
       19 . The method of  claim 18 , wherein said coacervating step results in the formation of nanospheres.  
   
   
       20 . The method of  claim 18 , wherein the respiratory syncytial virus antigens are selected from the group consisting of F, G, M, M2, SH, NS1, NS2, N, and P.