DNA vaccines increase immunogenicity of idiotypic tumor antigen by targeting novel fusion proteins to antigen-presenting cells.
Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC.
Fredriksen
Agnete B
AB
Institute of Immunology, University of Oslo, Rikshospitalet and Rikshospitalet University Hospital, Sognsvannsvn. 20, 0027 Oslo, Norway. a.b.fredriksen@medisin.uio.no
Sandlie
Inger
I
Bogen
Bjarne
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D019281:Dimerization; D018274:Electroporation; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D018448:Models, Immunological; D009101:Multiple Myeloma / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D010957:Plasmids; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000737:chemistry / Q000276:immunology*
D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA