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Development of the novel rabies vaccine by using gene-deficient virus

Research Project

Project/Area Number 23380179
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionGifu University

Principal Investigator

SUGIYAMA Makoto  岐阜大学, 応用生物科学部, 教授 (80196774)

Co-Investigator(Kenkyū-buntansha) ITO Naoto  岐阜大学, 応用生物科学部, 准教授 (20334922)
Co-Investigator(Renkei-kenkyūsha) INOUE Satoshi  国立感染症研究所, 獣医科学部, 室長 (90213157)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywords狂犬病ウイルス / ワクチン / 増殖欠損ウイルス / Mタンパク質 / Pタンパク質 / 狂犬病ワクチン / 遺伝子操作 / 遺伝子欠損 / 弱毒化変異
Research Abstract

The aim of this study was to generate a replication-defective (M gene-deficient) rabies virus strain by gene manipulation and to examine the potency of the strain as a rabies vaccine. Our preliminary data strongly suggested that the M gene-deficient virus could not sufficiently propagate in Vero cells stably expressing M protein. We generated a mixture of P- and M-gene deficient viruses by gene manipulation and examined the potency as a rabies vaccine. Theoretically, P- and M-gene deficient viruses will not produce progeny viruses unless the two different viruses infect an identical cell and complement the gene defect of each other. In fact, we found that the mixture of the P- and M-gene deficient viruses has high levels of safety and immunogenicity, indicating that the mixture is a promising candidate as the next-generation rabies vaccine.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (19 results)

All 2014 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (11 results) (of which Invited: 1 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Interaction of Rabies Virus P-Protein With STAT Proteins is Critical to Lethal Rabies Disease.2014

    • Author(s)
      Wiltzer, L, Okada, K, Yamaoka, S, Larrous, F, Kuusisto, HV, Sugiyama, M, Blondel, D, Bourhy, H, Jans, DA, Ito, N, Moseley, GW.
    • Journal Title

      Journal of Infectious Diseases

      Volume: in press Issue: 11 Pages: 1744-1753

    • DOI

      10.1093/infdis/jit829

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interaction of Rabies Virus P-Protein With STAT Proteins is Critical to Lethal Rabies Disease2013

    • Author(s)
      Wiltzer, L, Okada, K, Yamaoka, S, Larrous, F, Kuusisto, HV, Sugiyama, M, Blondel, D, Bourhy, H, Jans, DA, Ito, N, Moseley, GW
    • Journal Title

      J. Infect. Dis

      Volume: (in press)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of the rabies virus phosphoprotein gene in neuroinvasiveness2013

    • Author(s)
      Yamaoka, S, Ito, N, Ohka, S, Kaneda, S, Nakamura, H, Agari, T, Masatani, T, Nakagawa, K, Okada, K, Okadera, K, Mitake, H, Fujii, T, Sugiyama, M
    • Journal Title

      J. Virol

      Volume: 87(22) Issue: 22 Pages: 12327-38

    • DOI

      10.1128/jvi.02132-13

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a live rabies vaccine strain attenuated by multiple mutations and evaluation of its safety and efficacy2012

    • Author(s)
      Nakagawa, K, Ito, N, Masatani, T, Abe, M, Yamaoka, S, Ito, Y, Okadera, K, Sugiyama, M
    • Journal Title

      Vaccine

      Volume: 30(24) Issue: 24 Pages: 3610-7

    • DOI

      10.1016/j.vaccine.2012.03.044

    • Related Report
      2013 Final Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Generation of live rabies virus strain with high levels of safety and immunogenicity by mutations in nucleoprotein and glycoprotein2014

    • Author(s)
      Nakagawa, K., Ito, N., Mastani, T., Yamaoka, S., Okadera, K., Okada, K., Sugiyama, M
    • Organizer
      The 11th Awaji International Forum on Infection and Immunity
    • Place of Presentation
      Awaji Yumebutai International Conference Center, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Combination of attenuating mutations in rabies virus nucleoprotein and glycoprotein enhances safety of a live vaccine strain2014

    • Author(s)
      Nakagawa, K., Ito, N., Mastani, T., Yamaoka, S., Okadera, K., Okada, K., Sugiyama, M
    • Organizer
      4th Infection and Immunity conference Lorne Mantra
    • Place of Presentation
      Australia
    • Related Report
      2013 Final Research Report
  • [Presentation] Combination of attenuating mutations in rabies virus nucleoprotein and glycoprotein enhances safety of a live vaccine strain.2014

    • Author(s)
      Keisuke Nakagawa, Naoto Ito, Tatsunori Mastani, Satoko Yamaoka, Kota Okadera, Kazuma Okada, Makoto Sugiyama
    • Organizer
      4th Infection and Immunity conference
    • Place of Presentation
      Lorne Mantra, Australia
    • Related Report
      2013 Annual Research Report
  • [Presentation] N およびG 遺伝子に弱毒化変異を導入した狂犬病生ワクチン候補株の作出2012

    • Author(s)
      中川敬介, 伊藤直人, 山岡理子, 岡寺康太, 杉山誠
    • Organizer
      第60回日本ウイルス学会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] N およびG 遺伝子に弱毒化変異を導入した狂犬病ウイルス株の弱毒性状の解析2012

    • Author(s)
      中川敬介, 伊藤直人, 山岡理子, 岡寺康太, 杉山誠
    • Organizer
      第154回日本獣医学会
    • Place of Presentation
      岩手大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of rabies virus strain attenuated by multiple mechanisms2011

    • Author(s)
      Keisuke Nakagawa
    • Organizer
      International Union of Microbiological Socienties 2011 Congress
    • Place of Presentation
      Sapporo
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] N 遺伝子への変異導入による狂犬病ウイルス弱毒株の作出2011

    • Author(s)
      中川敬介, 伊藤直人, 正谷達謄, 山岡理子, 岡寺康太, 杉山誠
    • Organizer
      第152回日本獣医学会
    • Place of Presentation
      大阪府立大学
    • Related Report
      2013 Final Research Report
  • [Presentation] Generation of rabies virus strain attenuated by multiple mechanisms2011

    • Author(s)
      Nakagawa, K., Ito, N., Masatani, N., Abe, M. Yamaoka, S., Okadera, K., Sugiyama, M
    • Organizer
      XV International Congress of Virology
    • Place of Presentation
      Sapporo Convention Center
    • Related Report
      2013 Final Research Report
  • [Presentation] NおよびG遺伝子に弱毒化変異を導入した狂犬病ウイルス株の弱毒性状

    • Author(s)
      杉山 誠
    • Organizer
      第154回日本獣医学会学術集会
    • Place of Presentation
      盛岡市
    • Related Report
      2012 Annual Research Report
  • [Presentation] NおよびG遺伝子に弱毒化変異を導入した狂犬病ワクチン候補株の作出

    • Author(s)
      杉山 誠
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪市
    • Related Report
      2012 Annual Research Report
  • [Presentation] 狂犬病ウイルスの病原性発現機序に関する研究

    • Author(s)
      伊藤直人
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Patent(Industrial Property Rights)] 変異狂犬病ウイルス合成・増殖方法, 並びに狂犬病ワクチン製剤2012

    • Inventor(s)
      伊藤直人・杉山誠
    • Industrial Property Rights Holder
      国立大学法人岐阜大学・共立製薬株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-10-17
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 変異狂犬病ウイルス合成・増殖方法、並びに狂犬病ワクチン製剤2012

    • Inventor(s)
      伊藤直人、杉山 誠
    • Industrial Property Rights Holder
      伊藤直人、杉山 誠
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-229854
    • Filing Date
      2012-10-17
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 変異狂犬病ウイルス及びワクチン2011

    • Inventor(s)
      伊藤直人・杉山誠
    • Industrial Property Rights Holder
      国立大学法人岐阜大学・共立製薬株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2011-10-25
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 変異狂犬病ウイルス合成・増殖方法、並びに狂犬病ワクチン製剤2011

    • Inventor(s)
      杉山誠, 伊藤直人
    • Industrial Property Rights Holder
      岐阜大学
    • Industrial Property Number
      2011-234036
    • Filing Date
      2011-10-25
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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