Methods of use of viral vectors to deliver antigen to dendritic cells

Abstract

This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T-lymphocyte activity or may also be used as vaccines.

1 ) A method of delivering antigens to human dendritic cells in situ comprising: 
 a) providing a non-replicating viral vector which targets human dendritic cells, said viral vector comprising a gene sequence encoding for said antigen; and    b) exposing said human dendritic cells in situ to said non-replicating viral vector for a time sufficient to allow said antigen to be expressed on the surface of said human dendritic cells.    
   
   
       2 ) (canceled)  
   
   
       3 ) The method according to  claim 1 , wherein targeting of human dendritic cells is accomplished with a non-replicating influenza viral vector.  
   
   
       4 ) The method according to  claim 1 , wherein said non-replicating viral vector comprises recombinant nucleic acid.  
   
   
       5 ) The method according to  claim 1 , wherein said antigen is selected from the group consisting of tumor antigens, viral antigens, microbial antigens and autoimmune antigens.  
   
   
       6 ) The method according to  claim 5 , wherein said antigen comprises amino acid sequences from at least one strain of influenza virus.  
   
   
       7 ) The method according to  claim 1 , wherein said human dendritic cells are proliferating.  
   
   
       8 ) The method according to  claim 1 , wherein said human dendritic cells are non-proliferating.  
   
   
       9 ) The method according to claim  23  wherein said influenza virus is PR8.  
   
   
       10 - 29 . (canceled)  
   
   
       30 ) The method according to  claim 1 , wherein targeting of human dendritic cells is accomplished by modifying the non-replicating viral vector to encode for a protein, or part thereof, which is recognized by a receptor on human dendritic cells.