1998 Fiscal Year Final Research Report Summary
Investigation for the development of vaccine against hepatitis C virus
| Project/Area Number |
09670515
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MARUYAMA Toshiyuki University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (30219571)
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| Co-Investigator(Kenkyū-buntansha) |
YOTSUYANAGI Hiroshi Intemal Medicine Assistant Professor, 医学部・附属病院, 助手 (30251234)
MITSUI Hiroshi Intemal Medicine Assistant Professor, 医学部・附属病院, 助手 (30239280)
KOIKE Kazuhiko Intemal Medicine Associate Professor, 医学部・附属病院, 助教授 (80240703)
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| Project Period (FY) |
1997 – 1998
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| Keywords | HCV / peptide / vaccine / interferon / IgG subtype / prognostic ralue / mouse |
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| Research Abstract |
We have examined the murine T cell response to HCV core protein in terms of immunogenicity, the influence of H-2 linked genes, fine specificity, and relationship to in vivo antibody production by using recombinant HCV core protein which contains full length of entire core region. The HCV core protein was shown to have markedly lower immunogenicity compared to HBcAg on humoral and cellular response. The influence of H-2 linked genes on the humoral response to HCV core protein was discernible, and high responder (H-2f), intermediate responder (H-2b, s), and low responder (H-2k, d, p) haplotypes were identified. T cell recognition sites were defined by small (18 residue) synthetic peptides. Each strain recognized a predominant T cell determinant, and the fine specificity of this recognition process was dependent on the H-2 haplotype of the responding strain. For example, H-2f strain recognized p41-55, H-2b strain recognized p11-25, H-2s strain recognized p161-175 predominantly. When B10.M (H2-f) mice were primary immunized by p41-55 peptide, these mice had enough immune response after secondary immunization with HCV core protein. Therefore, p41-55 peptide is a good candidate for vaccine against HCV infection. These results that immune response to HCV core antigen is influenced by H-2 linked genes and that HCV core antigen is low immunogenic have clinical relevance most of patients with acute HCV infection produce lower antibodies against viral proteins in early phase.
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