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Study on development of a live attenuated vaccine for equine influenza infection using reverse genetics

Research Project

Project/Area Number 13556052
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Applied veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

GOTO Hideo  The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (50323639)

Co-Investigator(Kenkyū-buntansha) TAKADA Ayato  The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (10292062)
HORIMOTO Taisuke  The University of Tokyo, Institute of Medical Science, Associate professo, 医科学研究所, 助教授 (00222282)
KAWAOKA Yoshihiro  The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (70135838)
KONDO Takashi  Tochigi Branch, Equine Research Institute, Chief Researcher, 栃木支所・分子生物研究室, 主査(研究職)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2001: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywordsequine influenza virus / live vaccine / reverse genetics / attenuation
Research Abstract

Equine influenza is an important contagious respiratory disease of horses. In the field of veterinary medicine, equine influenza is recognized as a serious problem because it causes economical loss. Inactivated vaccine for equine influenza has been used to control infection; however its efficacy is not satisfactory.
The aim of this study is to develop a live attenuated vaccine for equine influenza infection. A live attenuated vaccine for influenza virus can be generated by insertion of a gene encoding target protein into genome of an attenuated virus. To this end we established a strategy to generate recombinant influenza virus that contained a foreign gene using reverse genetics.
The results we obtained were as follows.
1.Regions in the genome RNA segments required for their efficient incorporation into virus particle were found. The regions were located at the both ends of each genome segments and contained the protein encoding sequences. Thus we identified packaging signals in the genome segments of influenza A virus.
2.Identification of the packaging signals allowed us to produce a recombinant virus with a gene encoding foreign protein. By fusion of the packaging signals to the foreign genes, influenza A virus with the gene encoding the green fluorescent protein, the hemagglutinin and/or neuraminidase of influenza B virus or the glycoprotein of vesicular stomatitis virus was successfully generated.
3.Infection of the influenza A virus with the gene encoding influenza B virus glycoprotein induced immune response in mice.
So far, knowledge of mutations that lead to attenuation of influenza A virus has been accumulated. Therefore introduction of attenuation mutations and the system to generate recombinant influenza A virus enable us to establish a live attenuated vaccine not only for equine influenza but also other infections.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Watanabe T et al.: "Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity."J Virol. 75・14. 5656-5662 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goto H et al.: "Plasminogen-binding activity or neuraminidase determines the pathogenicity of influenza A virus."J Virol. 75・19. 9297-9301 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T et al.: "Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles."J Virol. 76・2. 767-773 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito T et al.: "Virulent influenza A viruses induce apoptosis in chickens."Virus Res. 84. 27-35 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T et al.: "Influenza A virus with defective M2 ion channel activity as a live vaccine."Virology. 299. 266-270 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi K et al.: "High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza."J Inf Dis. 188. 57-61 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii Y et al.: "Selective incorporation of influenza virus RNA segments into virions."Proc Natl Acad Sci USA. 100. 2002-2007 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horimoto T et al.: "Generation of influenza A viruses with chimeric (type A/B) hemagglutinins."J Virol. 77・14. 8031-8038 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T et al.: "Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes."J Virol. 77・19. 10575-10583 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda Y et al.: "Biological significance of the U residue at the -3 position of the mRNA sequences of influenza A viral segments PB1 and NA."Virus Res. 100. 153-157 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinya K et al.: "Characterization of a neuraminidase-deficient influenza a virus as a potential gene delivery vector and a live vaccine."J Virol. 78・6. 3083-3088 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horimoto T et al.: "A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model."Vaccine. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hatta M: "Influenza B virus requires BM2 protein for replication,"J Virol. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [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."J Virol. 75. 5656-5662 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goto H, Wells K, Takada A, Kawaoka Y.: "Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus."J Virol.. 75. 9297-9301 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y.: "Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles."J Virol. 76. 767-773 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito T, Kobayashi Y, Morita T, Horimoto T, Kawaoka Y.: "Virulent influenza A viruses induce apoptosis in chickens"Virus Res. 84. 27-35 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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."ViroIogy. 299. 266-270 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shiraishi K, Mitamura K, Sakai-Tagawa Y, Goto H, Sugaya N, Kawaoka Y.: "High frequency of resistant viruses harboring different mutations in amantadine-treated children with influenza."J Inf Dis. 188. 57-61 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujii Y, Goto H, Watanabe T, Yoshida T, Kawaoka Y.: "Selective incorporation of influenza virus RNA segments into virions."Proc Natl Acad Sci USA. 100. 2002-2007 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horimoto T, Takada A, Iwatsuki-Horimoto K, Hatta M, Goto H, Kawaoka Y.: "Generation of influenza A viruses with chimeric (type A/B) hemagglutinins."J Virol. 77. 8031-8038 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Watanabe T, Watanabe A, Noda T, Fujii Y, Kawaoka Y.: "Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes."J Virol. 77. 10575-10583 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Maeda Y, Goto H, Horimoto T, Takada A, Kawaoka Y.: "Biological significance of the U residue at the -3 position of the mRNA sequences of influenza A viral segments PB1 and NA."Virus Res. 100. 153-157 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinya K, Fujii Y, Ito H, Ito T, Kawaoka Y.: "Characterization of a neuraminidase-deficient influenza a virus as a potential gene delivery vector and a live vaccine."J 78. 78. 3083-3088 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horimoto T, Takada A, Iwatsuki-Horimoto K, Kawaoka Y.: "A protective immune response in mice to viral components other than hemagglutinin in a live influenza A virus vaccine model."Vaccine. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hatta M, Goto H, Kawaoka Y.: "Influenza B virus requires BM2 protein for replication."J Virol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Horimoto T.et al.: "Generation of influenza A viruses with chimeric (type A/B) hemagglutinins."J Virol.. 77・14. 8031-8038 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii Y et al.: "Selective incorporation of influenza virus RNA segments into virions"Proc.Natl.Acad.Sci. USA.. 100・4. 2002-2007 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shiraishi K et al.: "High Frequency of Resistant Viruses Harboring Different Mutations in Amantadine Treated Children with Influenza"J. Infect Dis.. (発表予定).

    • Related Report
      2002 Annual Research Report
  • [Publications] 白石京子 他: "抗インフルエンザ治療薬の問題点-理論的考察"インフルエンザ. 3・3. 201-207 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 堀本泰介 他: "ウイルスの病原性発現における糖タンパク質の役割"Molecular Medicine. 39. 212-226 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito T, et al.: "Generation of a highly pathogenic avian influenza A virus from an avirulent field isolate by passaging in chickens"J Virol.. 75・9. 4439-4443 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Goto H, et al.: "Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus"J Virol.. 79・19. 9297-9301 (2001)

    • Related Report
      2001 Annual Research Report

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

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