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 v...

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Veröffentlicht in:Molecular therapy 2006-04, Vol.13 (4), p.776-785
Hauptverfasser: Fredriksen, Agnete B, Sandlie, Inger, Bogen, Bjarne
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container_title Molecular therapy
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creator Fredriksen, Agnete B
Sandlie, Inger
Bogen, Bjarne
description 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.
doi_str_mv 10.1016/j.ymthe.2005.10.019
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subjects Animals
Antibodies
Antigen-Presenting Cells - immunology
Antigens
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Chemokines
Dimerization
Electroporation
Gene therapy
Histocompatibility Antigens Class II - immunology
Immunoglobulin Idiotypes - genetics
Immunoglobulin Idiotypes - immunology
Injections, Intramuscular
Lymphocytes
Lymphoma
Lymphoma, B-Cell - immunology
Mice
Mice, Inbred BALB C
Mice, SCID
Mice, Transgenic
Models, Immunological
Multiple myeloma
Multiple Myeloma - immunology
Neoplasms, Experimental - immunology
Neoplasms, Experimental - prevention & control
Plasmids
Proteins
Recombinant Fusion Proteins - immunology
Time Factors
Tumors
Vaccination
Vaccines
Vaccines, DNA - chemistry
Vaccines, DNA - immunology
title DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells
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