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Targeting Viral Antigens to CD11c on Dendritic Cells Induces Retrovirus-Specific T Cell Responses
Authors:Asim Ejaz  Christoph G. Ammann  Roland Werner  Georg Huber  Verena Oberhauser  Susanne H?rl  Simone Schimmer  Ulf Dittmer  Dorothee von Laer  Heribert Stoiber  Zoltán Bánki
Affiliation:1. Division of Virology, Innsbruck Medical University, Innsbruck, Austria.; 2. Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria.; 3. Institute of Virology, University of Duisburg-Essen, Essen, Germany.; Imperial College London, United Kingdom,
Abstract:Dendritic cells (DC) represent the most potent antigen presenting cells and induce efficient cytotoxic T lymphocyte (CTL) responses against viral infections. Targeting antigens (Ag) to receptors on DCs is a promising strategy to enhance antitumor and antiviral immune responses induced by DCs. Here, we investigated the potential of CD11c-specific single-chain fragments (scFv) fused to an immunodominant peptide of Friend retrovirus for induction of virus-specific T cell responses by DCs. In vitro CD11c-specific scFv selectively targeted viral antigens to DCs and thereby significantly improved the activation of virus-specific T cells. In vaccination experiments DCs loaded with viral Ag targeted to CD11c provided improved rejection of FV-derived tumors and efficiently primed virus-specific CTL responses after virus challenge. Since the induction of strong virus-specific T cell responses is critical in viral infections, CD11c targeted protein vaccines might provide means to enhance the cellular immune response to prophylactic or therapeutic levels.
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