Abstract
We designed and evaluated in HLA-class I transgenic mouse models a hepatitis C virus (HCV) T cell-based MVA vectored vaccine expressing three viral antigens known to be targets of potent CD8+- and CD4+-mediated responses. An accelerated (3 week-based) vaccination induced specific CD8+ T cells harboring two effector functions (cytolytic activity - both in vitro and in vivo- and production of IFNgamma) as well as specific CD4+ T cells recognizing all three vaccine antigens. Responses were long lasting (6 months), boostable by a fourth MVA vaccination and in vivo cross-reactive as demonstrated in a surrogate Listeria-based challenge assay. This candidate vaccine has now moved into clinical trials.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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CD8-Positive T-Lymphocytes / immunology
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Cross Reactions
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Genetic Vectors
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HLA-A2 Antigen / genetics
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HLA-B7 Antigen / genetics
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Hepacivirus / genetics
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Hepacivirus / immunology*
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Hepatitis C Antigens / genetics
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Humans
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Immunization Schedule*
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Immunization, Secondary
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Listeria monocytogenes / genetics
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Listeria monocytogenes / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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T-Lymphocytes / immunology*
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T-Lymphocytes, Cytotoxic / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Vaccinia virus / genetics
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Viral Hepatitis Vaccines / administration & dosage*
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Viral Hepatitis Vaccines / genetics
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Viral Hepatitis Vaccines / immunology
Substances
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HLA-A2 Antigen
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HLA-B7 Antigen
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Hepatitis C Antigens
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Vaccines, Synthetic
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Viral Hepatitis Vaccines