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Development of influenza live vaccine by reverse genetics

Research Project

Project/Area Number 13557023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Virology
Research InstitutionThe University of Tokyo

Principal Investigator

KAWAOKA Yoshihiro  University of Tokyo, IMS, Professor, 医科学研究所, 教授 (70135838)

Co-Investigator(Kenkyū-buntansha) HORIMOTO Taisuke  University of Tokyo, IMS, Associate Professor, 医科学研究所, 助教授 (00222282)
GOTO Hideo  University of Tokyo, IMS, Assistant Professor, 医科学研究所, 助手 (50323639)
TAKADA Ayato  University of Tokyo, IMS, Assistant Professor, 医科学研究所, 助手 (10292062)
OSUMI Kunio  The Chemo-Sero Therapeutic Research Institute, The director, 第一製剤部長
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2001: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywordsinfluenza virus / reverse genetics / live vaccine / A型インフルエンザウイルス / M2膜蛋白質 / M2蛋白質 / 膜貫通領域
Research Abstract

Influenza virus is a highly infectious respiratory pathogen of birds and mammals, including human. It often produces significant mobidity and mortality in humans. Current methods of immunization against influenza virus include parental administration of inactivated influenza virus vaccines, which reduces the incidence of clinical illness in healthy subjects. But in some cases, immunization with inactivated vaccines is associated with very low protection rates or short protection periods.
Another promising approach to vaccination is the use of live-attenuated influenza viruses. Theses vaccines have shown considerable promise in ongoing clinical trials. However, it has been concerned that the pathogenesis happened to recovered during their replication.
We propose an alternative approach to the design of live virus vaccines, one that relies on alteration of the influenza A virus M2 protein which is responsible for ion channel activity. It did not show appreciable growth defect in cell culture, although its growth was attenuated in mice. It has shown that this M2 ion channel defective mutant virus protected mice against challenge with lethal doses of influenza virus, indicating the potential or incorporating this M2 alteration in a live influenza vaccine as one of the attenuating mutations.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All 2002 2001 Other

All Journal Article (8 results) Publications (7 results)

  • [Journal Article] Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles.2002

    • Author(s)
      Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y.
    • Journal Title

      Journal of Virology 76

      Pages: 767-773

    • NAID

      120000968073

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza A virus with defective M2 ion channel activity as a live vaccine.2002

    • Author(s)
      Watanabe T, Watanabe S, Kida H, Kawaoka Y
    • Journal Title

      Virology 299

      Pages: 266-270

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles.2002

    • Author(s)
      Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y.
    • Journal Title

      Journal of Virology

      Pages: 767-773

    • NAID

      120000968073

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza A virus with defective M2 ion channel activity as a live vaccine.2002

    • Author(s)
      Watanabe T, Watanabe S, Kida H, Kawaoka Y.
    • Journal Title

      Virology 299

      Pages: 266-270

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity.2001

    • Author(s)
      Watanabe T, Watanabe S, Ito H, Kida H, Kawaoka Y
    • Journal Title

      Journal of Virology 75

      Pages: 5656-5662

    • NAID

      120000965795

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza virus NS1 protein induces apoptosis in cultured cells.2001

    • Author(s)
      Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y., Hinshaw VS.
    • Journal Title

      Journal of Virology 75

      Pages: 7875-7881

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity.2001

    • Author(s)
      Watanabe T, Watanabe S, Ito H, Kida H, Kawaoka Y.
    • Journal Title

      Journal of Virology 75

      Pages: 5656-5662

    • NAID

      120000965795

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Journal Article] Influenza virus NS1 protein induces apoptosis in cultured cells.2001

    • Author(s)
      Schultz-Cherry S, Dybdahl Sissoko N, Neumann G, Kawaoka Y, Hinshaw VS.
    • Journal Title

      Journal of Virology 75

      Pages: 7875-7881

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Watanabe S, Kida H, Kawaoka Y: "Influenza A virus with defective M2 ion channel activity as a live vaccine"Virology. 299. 266-270 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y: "Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles"Journal of Virology. 76. 767-773 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Neumann G, Kawaoka Y: "Reverse genetics of influenza virus"Virology. 287. 243-250 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Neumann G, Kawaoka Y: "Generation of influenza A virus from cloned cDNAs-historical perspective and outlook for the new millennium"Review of Medical Virology. 12. 13-30 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Neumann G, Kawaoka Y: "Synthesis of Influenza Virus : New Impetus from an Old Enzyme, RNA Polymerase I"Virus Research. 82. 153-158 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Neumann G, Whitt MA, Kawaoka Y: "A Decade After the Generation of a Negative-Sense RNA Virus From Cloned cDNA-What Have We Learned?"Journal of General Virology. 83. 2635-2662 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Watanabe T, Watanabe S, Ito H, Kida H, Kawaoka Y.: "Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity"Journal of Virology. 75. 5656-5662 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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