Abstract
Multiepitope-based vaccines against hepatitis C virus (HCV) were designed in the form of three minigenes encompassing four domains of the NS3, NS4 and NS5B proteins that contain multiple class I/II restricted epitopes. The polyEp-WT minigene encodes all four domains in fusion, the polyEp-C minigene encodes the same fusion but optimised for mammalian translation and the polyEp-E3 minigene has an additional endoplasmic reticulum targeting sequence. Whereas the minigenes vectorised by DNA were poorly immunogenic, adenovirus vectorisation induced strong and broader IFNgamma-ELISpot and CTL responses in HLA-A2 transgenic mice. In addition, polyEp-WT and polyEp-E3 responses were found cross-reactive in a recombinant Listeria-NS3-based surrogate challenge. This study illustrates the potency of vectorised minigenes in the field of HCV vaccine development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Animals
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Colony Count, Microbial
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Epitopes / genetics
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Epitopes / immunology
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Genetic Vectors
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Hepacivirus / genetics
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Hepacivirus / immunology*
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Interferon-gamma / biosynthesis
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Listeria / genetics
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Listeria / growth & development
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Liver / immunology
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Liver / microbiology
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Mice
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Mice, Transgenic
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Spleen / immunology
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Spleen / microbiology
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T-Lymphocytes, Cytotoxic / immunology
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Transduction, Genetic
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
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Viral Hepatitis Vaccines / genetics
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Viral Hepatitis Vaccines / immunology*
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / immunology
Substances
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Epitopes
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NS3 protein, hepatitis C virus
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NS4 protein, hepatitis C virus
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Vaccines, Synthetic
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Viral Hepatitis Vaccines
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Viral Nonstructural Proteins
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Interferon-gamma
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NS-5 protein, hepatitis C virus