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Investigation for the development of vaccine against hepatitis C virus

Research Project

Project/Area Number 09670515
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo

Principal Investigator

MARUYAMA Toshiyuki  University of Tokyo Hospital Assistant Professor, 医学部・附属病院, 助手 (30219571)

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)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHCV / peptide / vaccine / interferon / IgG subtype / prognostic ralue / mouse / エペトープ / IgGサブクラス / C型肝炎 / ペプタイト / 免疫応答
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.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] T.Maruyama: "High prevalence of prec wild type HBU DNA and HBeAgIFCs---"Hepatology. 27. 245-253 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Mitsui: "Thrombin activates two stress-activated protein kinales"Hepatology. 27. 1362-1367 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Koike: "Sialadeniti* resembling Sjogren's syndrome in hopatis C virus"Proc.Natl.Acad.Sci.USA. 94. 233-236 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Yotsuyanagi: "Persistent viremia after recovery from self limited"Hepatology. 27. 1377-1382 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T. Maruyama. et al.: "High prevalence of pre-c wild type HBV-DNA and HBeAg/ICs in patients with chronic hepatis B often seroconversion."Hepatology. 27. 245-253 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Mitsui. et al.: "Thrombin activates two stress-activated protein kinases, c-jun, N terminal kinase and p38 in Hep G2 cells"Hepatology. 27. 1362-1367 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K. Koike et al.: "Sialadenitis resembling Sjogren's syndrome in hepatitis C virus envelope gene transgenic mice"Proc. Natl. Acad. Sci. USA. 94. 233-236 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H. Yotsuyanagi et al.: "Persistent viremia after recovery from self-limited acute hepatitis B"Hepatology. 27. 1377-1382 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Maruyama T,: "High prevalence of pre・c wild type HBV・DNA" Hepatology. 27. 245-253 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mitsui H,: "Thrombin activates two stress-activated protein kinases" Hepatology. 27. 1362-1367 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mitsui H: "Dependence of Gal 2 mediated G1/S all cycle progression" J.Biol. Clemistry. 272. 4904-4910 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yotsuyanagi: "Persistent viremia after recovery from self-limited AH-B" Hepatology. 27. 1377-1382 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Koike K: "Sialadenitis resembling Sjogren's syndrome" Proct.Natl. Acad. Scier USA. 94. 233-236 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Maruyama: "Precore Wild type DNA and immune complexes persisl in chronic hepatitis B after seroconversion" Hepatology. 27. 245-253 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Koike: "Sialadenitis resembling Sjogren's syndrome in hepatitis C virus envelepe gene transgenic mice" Proc Natl Acad Science U.S.A.94. 233-236 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Moriya: "Hepatitis C virus core protein induces hepatis steatosis in transgenic mice" J.Gen.Virology. 78. 1527-1531 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Mitsui: "Depen dence of Ga12 mediated G1/S cell cycle progression on both Ras/Mapk and Ras pathways" J.Biol.Chem.272. 4904-4910 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Mitsui: "Thrombin activates two stress activated protein kinases.C-Jun N terminal kinase γ-Hey G2 cells" Hepatology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Hashimoto: "Protaglandins induce proliferation of rat hepatocytes through a prostoglundin E2 reeapter EP3 sultype" Am J.Pbysiol. 272. G597-G604 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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