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Development of flavivirus-cross-reactive subunit vaccines

Research Project

Project/Area Number 09044344
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research .
Research Field Virology
Research InstitutionNational Institute of Infectious Diseases (1998)
Kinki University (1997)

Principal Investigator

KURANE Ichiro  National Institute of Infectious Diseases・Department of Virology I,Director, ウイルス第一部, 部長 (90278656)

Co-Investigator(Kenkyū-buntansha) TAKASAKI Tomohiko  National Institute of Infectious Diseases Department of Virology I,Senior Scient, ウイルス第一部, 主任研究官 (20221351)
ENNIS Franci  マサチューセッツ大学, 医学部, 教授
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsFlavivirus / Dengue virus / Japanese encephalitis virus / Vaccine / Cytotoxic T lymphocyte / デンブウイルス / デンフウウルス / エピトープ
Research Abstract

The aim of the present researh is to examine whether it is possible to develop vaccines which induce protective immunity against multiple flaviviruses. We analyzed flavivirus-cross-reactive T lymphocyte responses. We first analyzed CD8+ cytotoxic T lymphocytes (CTL) responses to the epitope on the NS3 protein of dengue viruses. Mice were infected with dengue virus type 2. CTL induced by the infection recognized the epitope located on the amino acids 289 to 306 on the NS3. Most of the CTL recognizing this epitope were cross-reactive for dengue virus type 2 and type 4. When mice were infected with dengue virus type, CTL were cross-reactive for all the 4 serotyoes of dengue viruses, but also recognized the epitope located on the amino acids 289 to 306 on the NS3. CTL clones established from the mice infected with dengue virus type 3 were cross-reactive for other flaviviruses such as Kunjin virus and Murray Valley encephalitis virus. It is generally accepted that virus-specific CTL are important for recovery fromvirus infections. Thus, the results suggest that development of vaccines which induce protective immunity against multiple flaviviruses may be possible. It is of interest that flavivirus-cross-reactivity differs depending of the serotype of the infecting dengue viruses. This result is consistent with the observation that rate of the development of dengue hemorrhagic fever differs depending on the serotypes in the first and second dengue viral infections. Human CD4+ T cell clones established from Japanese encephalitis-immune donors Included those cross-reactive for Japanese encephalitis and West Nile viruses. Thus, flavivirus-cross-reactive T cells are also present. in humans.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Anuga Mathew: "Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection" Journal of Virology. 72. 3999-4004 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirokuni Aihara: "Establishment and characterization of Japanese encephalitis virus-specific, human CD4^+ T-cell clones : flavivirus-cross-reactivity, protein recognition and cytotoxic activity" Journal of Virology. 72. 8032-8036 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Anne C.Spaulding: "Analysis of Murine CD8^+ T-cell clones specific for the dengue virus NS3 protein : flavivirus cross-reactivity and influence of infecting serotype" Journal of Virology. 73. 398-403 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 倉根一郎: "日本脳炎ワクチン" 化学療法の領域. 14(11). 59-65 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 倉根一郎: "デング熱・デング出血熱" Bio Clinica. 14. 78-82 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Anjua Mathew et al.: "Predominance of CTL responses to serotyp crossreactive epitopes on nonstructural protein following natural secondary dengue virus infection." Journal of Virology. 72. 3999-4004 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirokuni Aihara et al.: "Establishment and characterization of Japanese encephalitis virus-specific, human CD4+ T cell clones : flavivirus cross-reactivity, protein recognition and cytotoxic activity." Journal of Virology. 72. 8032-8936 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Anne Spaulding et al.: "Analysis of murine CD8+ T cell clones specific for the dengue virus NS3 protein : flavivirus cross-reactivity and influence of the infecting serotype." Journal of Virology. 73. 398-403 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichiri Kurane: "Japanese encephalitis Vaccine." Field of Chemotherapy. 14. 1963-1969 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ichiro Kurane: "Dengue fever/Dengue hemorrhagic fever." Bio Clinica. 14. 78-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Anuja Mathew: "Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection" Journal of Virology. 72・5. 3999-4004 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirokuni Aihara: "Establishment and characterization of Japanese encephalitis virus-speafic, human CD4^+ T-cell clones : flavivirus cross-reactivity, protein recognition and cytotoxic activity" Journal of Virology. 71・10. 8032-8036 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Anne C.Spaulding: "Analysis of Murine CD8^+ T-cell clones specific for the dengue virus NS3 protein : flavivirus cross-reactivity and influence of infecting serotype" Journal of Virology. 73・1. 398-403 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 倉根一郎: "日本脳炎ワクチン" 化学療法の領域. 14・11. 59-65 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 倉根一郎: "デング熱・デング出血熱" Bio Clinica. 14・1. 78-82 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 倉根 一郎, 小西 英二: "日本脳炎ウイルス遺伝子を含む組み換えポックスウイルスに対するヒトT細胞免疫応答" Neuro・Infection. 2巻・1号. 141-142 (1997)

    • Related Report
      1997 Annual Research Report

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

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