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Development of T-cell vaccine for hepatitis C virus

Research Project

Project/Area Number 07557047
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Gastroenterology
Research InstitutionJichi Medical School

Principal Investigator

IMAWARI Michio  Jichi Medical School, Department of Medicine, Professor, 医学部, 教授 (70134228)

Co-Investigator(Kenkyū-buntansha) KANEKO Takashi  Jichi Medical School, Department of Medicine, Associate, 医学部, 助手 (10254913)
MORIYAMA Takashi  Jichi Medical School, Department of Medicine, Instructor, 医学部, 講師 (10240706)
安藤 量基  自治医科大学, 医学部, 助手 (20265276)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥9,600,000 (Direct Cost: ¥9,600,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1995: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordshepatitis C virus / hepatitis C / cytotoxic T cell / DNA vaccine / GM-CSF / ヘルパーT細胞 / HLAB44 / ワクチン / インターロイン12
Research Abstract

We tried to develop T-cell vaccine to prevent and treat hepatitis C virus (HCV) infection. We established cytotoxic T cell clones from peripheral blood lymphocytes of two HLA B44-positive patients with chronic HCV infection that recognize HCV core antigen 88-96 as a minimal and optimal epitope. We demonstrated that positions 4 and 6 of the 9 amino acid epitope were important for the binding of the epitope and T-cell antigen receptors of the CTL clones. When amino acids at positions 4 and 7 were substituted by other amino acids, a wild type epitope for type 1b and 2a HCV (NEGLGWAGW) and a variant type for 2b HCV (NEGCGWMGW) were recognized most efficitntly by CTL slones. HCV DNA that express HCV core antigen in the tranfected mammalian cells induced HCV-specific CTL when the DNA was injected directly into the spleen of mice. Intramuscular injection of the DNA did not induce CTL in either mice or chimpanzees.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Kita, Hiroto: "A minimal and optimal cytotoxic T cell epitope within hepatitis C virus nucleoprotein" Journal of General Virology. 76. 3189-3193 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroishi, Kazumasa: "Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection" Hepatology. 25. 702-712 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ando, Kazuki: "Perforin,Fas/Fas ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. 158. 5283-5291 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kaneko, Takashi: "Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist borne by a variant hepatitis C virus epitope" European Journal of Immunology. 27. 1782-1787 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kita, Hiroto: "A minimal and optimal cytotoxic T cell epitope within hepatitis C virus nucleoprotein." Journal of General Virology. 76. 3189-3193 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroishi, Kazumasa: "Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection." Hepatology. 25. 702-712 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ando, Kazuki: "Perforin, Fas/Fas ligand, TNF-alpha pathways as specific and bystander killing mechanisms of hepatitis Cvirus-specific human CTL" Journal of Immunology. 158. 5283-5291 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kaneko, Takashi: "Impaired induction of cytotoxic T lymphocytes by antagonis of a weal agonist borne by a variant hepatitis C virus epitope" European Journal of Immunology. 27. 1782-1787 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hiroishi,Kazumasa: "Cytotoxic T lymphocyte response and viral load hepatitis C virus infection" Hepatology. 25. 702-712 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ando,Kazuki: "Perforin,Fas/Fas ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. 158. 5283-5291 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaneko,Takashi: "Impaired induction of cytotoxic T lymphocytes by antagonism of a weak agonist bome by a variant hepatitis Cvirus epitope" European Journal of Immunology. 27. 1782-1787 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kaneko,Takashi: "Three new cytotoxic T cell epitopes identified within the hepatitis C virus nucleoprotein" Journal of General Virology. 77. 1305-1309 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroishi,Kazumasa: "Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection" Hepatology. 25(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ando,Kazuki: "Perfporin,Fas/Fas ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Arai,Hiroyoshi: "Symptomatic myopathy associated with interferon therapy for chronic hepatitis C" Lancet. 345. 582-582 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kita,Hiroto: "A helper T-cell antigen enhances generation of hepatitis C virus-specific cytotoxic T lymphocytes in vitro" Journal of Medical Virology. 45. 386-391 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Harase,Ichiro: "Immune response to hepatitis C virus core protein in mice" Immunology and Cell Biology. 73. 346-352 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kita,Hiroto: "HLAB44-restricted cytotoxic T lymphocyte responses to the peptides of HCV nucleoprotein residues 81-100 in patients with chronic hepatitis C" Journal of Gastroenterology. 30. 809-812 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kita,Hiroto: "A minimal and optimal cytotoxic T cell epitope within hepatitis C virus nucleoprotein" Journal of General Virology. 76. 3189-3193 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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