Somatic Transgene Immunization and Related Methods

Abstract

The invention provides a method for stimulating an immune response by administering to a lymphoid tissue a nucleic acid molecule comprising an expression element operationally linked to a nucleic acid sequence encoding one or more heterologous epitopes. The heterologous epitope can be inserted into a complementarity-determining region of an immunoglobulin molecule. The invention also provides a nucleic acid molecule comprising a hematopoietic expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide. The invention additionally provides a method of treating a condition by administering a nucleic acid molecule comprising a hematopoietic cell expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide, wherein the nucleic acid molecule is targeted to a hematopoietic cell.

1 - 33 . (canceled) 
     
     
         34 . A method for stimulating an immune response, comprising:
 transfecting B cells ex vivo with a plasmid comprising a nucleic acid encoding a B cell-specific expression element operationally linked to a nucleic acid sequence encoding an immunoglobulin molecule containing said one or more heterologous epitopes, wherein said epitope is inserted within a complementarity-determining region (CDR) of said immunoglobulin molecule; and   intravenously administering said transfected B cell to an individual to stimulate an immune response.   
     
     
         35 . The method of claim  1 , wherein said B cell is derived from blood or a lymphoid tissue selected from the group consisting of spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT), tonsils, Payer's patches, nasal-associated lymphoid tissue (NALT), Waldeyer's ring, and urogenital lymphoid tissue. 
     
     
         36 . The method of claim  1 , wherein at least one of said one or more heterologous epitopes comprises a T cell epitope. 
     
     
         37 . The method of claim  1 , wherein said heterologous epitopes comprise two T cell epitopes. 
     
     
         38 . The method of claim  4 , wherein said T cell epitopes are selected from the group consisting of a CD4 epitope and a CD8 epitope, two CD4 epitopes and two CD8 epitopes. 
     
     
         39 . The method of claim  1 , wherein said one or more epitopes stimulates an antibody response. 
     
     
         40 . The method of claim  1 , wherein said one or more epitopes stimulates a CD4 T cell response. 
     
     
         41 . The method of claim  1 , wherein said one or more epitopes stimulates a CD8 T cell response. 
     
     
         42 . The method of claim  1 , wherein said epitope stimulates a CD4 T cell response and a CD8 T cell response. 
     
     
         43 . The method of claim  1 , wherein one of said epitopes stimulates an antibody response and one or more second epitopes stimulates a CD4 T cell response and a CD8 T cell response. 
     
     
         44 . The method of claim  1  wherein said immunoglobulin comprises a variable region. 
     
     
         45 . The method of claim  11 , wherein said variable region is a heavy chain variable region. 
     
     
         46 . The method of claim  11 , wherein said variable region is a light chain variable region. 
     
     
         47 . The method of claim  1 , wherein said immunoglobulin molecule comprises a heavy chain. 
     
     
         48 . The method of claim  11 , wherein said immunoglobulin molecule comprises a light chain.