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 . A method for stimulating an immune response, comprising 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. 
     
     
         2 . The method of  claim 1 , wherein said lymphoid tissue is 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. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein said epitope stimulates an antibody response. 
     
     
         6 . The method of  claim 1 , wherein said epitope stimulates a CD4 T cell response. 
     
     
         7 . The method of  claim 1 , wherein said epitope stimulates a CD8 T cell response. 
     
     
         8 . The method of  claim 1 , wherein said epitope stimulates a CD4 T cell response and a CD8 T cell response. 
     
     
         9 . 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. 
     
     
         10 . The method of  claim 1 , wherein said epitope is expressed as a fusion with a cytokine. 
     
     
         11 . The method of  claim 10 , wherein said cytokine is selected from the group consisting of granulocyte-macrophage colony-stimulating factor, interleukin-2, interleukin-4, interferon-γ, interleukin-5, interleukin-6, interleukin-10 and interleukin-12. 
     
     
         12 . The method of  claim 1 , wherein said nucleic acid molecule encodes an immunoglobulin molecule containing said heterologous epitope, wherein said epitope is inserted within a complementarity-determining region (CDR) of said immunoglobulin molecule. 
     
     
         13 . The method of  claim 12 , wherein said immunoglobulin comprises a variable region. 
     
     
         14 . The method of  claim 13 , wherein said variable region is a heavy chain variable region. 
     
     
         15 . The method of  claim 13 , wherein said variable region is a light chain variable region. 
     
     
         16 . The method of  claim 12 , wherein said immunoglobulin molecule comprises a heavy chain. 
     
     
         17 . The method of  claim 12 , wherein said immunoglobulin molecule comprises a light chain. 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A nucleic acid molecule comprising a hematopoietic cell expression element operationally linked to a nucleic acid sequence encoding one or more heterologous epitopes, wherein said nucleic acid sequence encodes an immunoglobulin molecule containing said one or more epitopes and wherein said one or more epitopes is inserted within a complementarity-determining region (CDR) of said immunoglobulin molecule. 
     
     
         23 . The nucleic acid molecule of  claim 22 , wherein said immunoglobulin comprises a variable region. 
     
     
         24 . The nucleic acid molecule of  claim 23 , wherein said variable region is a heavy chain variable region. 
     
     
         25 . The nucleic acid molecule of  claim 23 , wherein said variable region is a light chain variable region. 
     
     
         26 . The nucleic acid molecule of  claim 22 , wherein said one or more epitopes is inserted in two CDRs. 
     
     
         27 . The nucleic acid molecule of  claim 22 , wherein said epitope is expressed as a fusion with a cytokine. 
     
     
         28 . The nucleic acid molecule of  claim 27 , wherein said cytokine is selected from the group consisting of granulocyte-macrophage colony-stimulating factor, interleukin-2, interleukin-4, interferon-γ, interleukin-5, interleukin-6, interleukin-10 and interleukin-12. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . A method of treating a condition, comprising administering a nucleic acid molecule comprising a hematopoietic cell expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide selected from the group consisting of hormone, cytokine, clotting factor and immunoglobulin.