Abstract
To develop a vaccine against hepatitis C virus, we synthesized four long peptides from nonstructural proteins NS3, NS4 and NS5B containing HLA-class I and class II epitopes mainly inducing responses in natural infection. In HLA-A2.1 transgenic mice, the four peptides primed higher CTL responses to 6:7 minimal HLA-A2 epitopes than those induced by the minimal epitopes. HLA-A2.1/HLA-DR1 transgenic mice immunized with one peptide, containing a class II epitope implicated in viral resolution, developed IFNgamma-producing CD4+-T and CD8+-T cells. These peptides recalled HCV-specific IFNgamma-producing cells from HCV-infected patients' PBMC. This support the selection of these domains for inclusion in a vaccine formulation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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Cytotoxicity, Immunologic
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Epitopes / immunology*
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Epitopes, T-Lymphocyte / immunology
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HLA-A2 Antigen / genetics
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HLA-DR1 Antigen / genetics
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Hepacivirus / immunology*
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Hepatitis C / immunology
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Humans
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Immunologic Memory*
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Interferon-gamma / biosynthesis
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Mice
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Mice, Transgenic
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Middle Aged
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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Viral Hepatitis Vaccines / immunology*
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Viral Nonstructural Proteins / administration & dosage
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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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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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HLA-DR1 Antigen
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NS3 protein, hepatitis C virus
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NS4 protein, hepatitis C virus
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Recombinant Proteins
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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