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Development of the novel therapeutic vaccine using persistent viral hepatitis infection model

Research Project

Project/Area Number 23591004
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Metropolitan Institute of Medical Science

Principal Investigator

KIMURA Kiminori  公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (70397339)

Co-Investigator(Kenkyū-buntansha) NAGAKI Masahito  岐阜大学, 医学部, 非常勤講師 (30293559)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHCV / ワクチン / 治療ワクチン / 慢性肝炎 / サイトカイン
Research Abstract

Chronic hepatitis C, which is caused by infection with the hepatitis C virus (HCV), is a global health problem. Using a mouse model of hepatitis C, we examined the therapeutic effects of a recombinant vaccinia virus (rVV) that encodes an HCV protein. Immunization with one rVV strain (rVV-N25), which encoded nonstructural HCV proteins, suppressed serum inflammatory cytokine levels and alleviated the symptoms of pathological chronic hepatitis C within 7 days after injection. Furthermore, HCV protein levels in liver tissue also decreased in a CD4 and CD8 T-cell-dependent manner. Consistent with these results, we showed that rVV-N25 immunization induced a robust CD8 T-cell immune response that was specific to the HCV nonstructural protein 2. In addition, we propose that rVV-N25 could be developed as an effective therapeutic vaccine.

Report

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

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (11 results) (of which Peer Reviewed: 11 results) Presentation (14 results)

  • [Journal Article] Should we try antiviral therapy for hepatitis C virus infection with pyoderma gangrenosum-like lesions?2014

    • Author(s)
      Kiminori Kimura
    • Journal Title

      Hepatology research

      Volume: 44 Issue: 2 Pages: 173-175

    • DOI

      10.1111/hepr.12158

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Should we try anti-viral therapy for hepatitis C virus infection with pyoderma gangrenosum-like lesions?2013

    • Author(s)
      Kimura k
    • Journal Title

      Hepatology Research

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Kinetics of peripheral hepatitis B virus-specific CD8(+) T cells in patients with onset of viral reactivation.2012

    • Author(s)
      Aoki J, Kowazaki Y, Ohtsuki T, Okamoto R, Ohashi K, Hayashi S, Sakamaki H, Kohara M, Kimura K
    • Journal Title

      J Gastroenterol

      Volume: 47 Issue: 6 Pages: 22-22

    • DOI

      10.1007/s00535-012-0676-y

    • NAID

      10031184063

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver2012

    • Author(s)
      Sekiguchi S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K, Kohara M.
    • Journal Title

      PLoS One

      Volume: 7(12)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The development of therapeutic vaccine for hepatitis C virus2012

    • Author(s)
      Kimura K, Kohara M. Gan To Kagaku Ryoho.
    • Journal Title

      Review

      Volume: Oct;39(10) Pages: 1451-7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunization with a recombinant vaccinia virus that encodes nonstructural proteins of the hepatitis C virus suppresses viral protein levels in mouse liver.2012

    • Author(s)
      Sekiguchi, S, Kimura K, Chiyo T, Ohtsuki T, Tobita Y, Tokunaga Y, Yasui F, Tsukiyama-Kohara K, Wakita T, Tanaka T, Miyasaka M, Mizuno K, Hayashi Y, Hishima T, Matsushima K and Kohara M.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 12 Pages: e51656-e51656

    • DOI

      10.1371/journal.pone.0051656

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The development of therapeutic vaccine for hepatitis C virus2012

    • Author(s)
      Kimura k, kohara m
    • Journal Title

      Gan To Kagaku Ryoho

      Volume: 39(10) Pages: 1451-7

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] An experimental mouse model for hepatitis C virus2011

    • Author(s)
      Kimura K, Kohara M.
    • Journal Title

      Exp Anim

      Volume: 60(2) Pages: 93-100

    • NAID

      10029550066

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of interleukin-18 in intrahepatic inflammatory cell recruitment in acute liver injury2011

    • Author(s)
      Kimura K, Sekiguchi S, Hayashi S, Hayashi Y, Hishima T, Nagaki M, Kohara M.
    • Journal Title

      J Leukoc Biol

      Volume: Mar;89(3) Issue: 3 Pages: 433-42

    • DOI

      10.1189/jlb.0710412

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] An experimental mouse model for hepatitis C virus.2011

    • Author(s)
      Kimura K and Kohara M
    • Journal Title

      Exp. Animal.

      Volume: 60(2) Pages: 93-100

    • NAID

      10029550066

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of interleukin-18 in intrahepatic inflammatory cells recruitment in acute liver injury.2011

    • Author(s)
      Kimura K, Sekiguchi S, Hayashi S, Hayashi y, Hishima T, Nagaki M, Kohara M.
    • Journal Title

      Journal of Leukocyte Biology

      Volume: 89(3) Pages: 433-42

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] The efficac y of entecavir in patients with hepatitis B viru s reactivation after allo-HSCT2013

    • Author(s)
      Yoshioka K, Kimura K, et al.
    • Organizer
      第75回日本血液学会学術集会、Poster presentation PS-1 -374
    • Place of Presentation
      札幌
    • Year and Date
      2013-11-09
    • Related Report
      2013 Final Research Report
  • [Presentation] 造血幹細胞移植後のHBV再活性化における宿主の免疫応答の解析2013

    • Author(s)
      木村公則、坂巻壽他
    • Organizer
      第17回日本肝臓学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-10-09
    • Related Report
      2013 Final Research Report
  • [Presentation] Ki netics of peripheral hepatitis B virus-specific C D8+ T cells in patients with onset of viral rea ctivation. Poster presentation2013

    • Author(s)
      Kimura K, Aoki J, Kowazaki Y, et al.
    • Organizer
      AASLD (Americ an Association for the study of Liver Disease s) Single topic Conference
    • Place of Presentation
      Washington DC
    • Year and Date
      2013-03-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Tissue macrophages are responsible for inflammatory liver disease in the hepatitis C virus transgenic mice2013

    • Author(s)
      Kiminori Kimura, Takahiro Otsuki, Yuko Tokunaga, Michinori Kohara
    • Organizer
      アメリカ肝臓学会
    • Place of Presentation
      ワシントン、USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] KINETICS OF PERIPHERAL HEPATITIS B VIRUS-SPECIFIC CD8+ T CELLS IN PATIENTS WITH ONSET OF VIRAL REACTIVATION2013

    • Author(s)
      Kimura k, Aoki J, Kohara m
    • Organizer
      AASLD
    • Place of Presentation
      ワシントン
    • Related Report
      2012 Research-status Report
  • [Presentation] Kinetics of Peripheral Hepatitis B Virus-specific CD8+ T Cells in Patients with Onset of Viral Reactivation2012

    • Author(s)
      Kimura k, Aoki J, Kohara m
    • Organizer
      AASLD
    • Place of Presentation
      ボストン
    • Related Report
      2012 Research-status Report
  • [Presentation] C型慢性肝炎に対する治療ワクチンの有効性について2012

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本肝臓学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] HBV再活性化時における宿主免疫動態の解析2012

    • Author(s)
      木村公則、青木淳、林星舟
    • Organizer
      日本肝臓学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Immunization with a recombinant vaccinia virus encoding a nonstructural protein of the hepatitis C virus ameliorates chronic hepatitis in the liver of transgenic mice2012

    • Author(s)
      Kimura k, Kohara m
    • Organizer
      keystone symposium "Immunological Mechanisms of Vaccination
    • Place of Presentation
      カナダ
    • Related Report
      2012 Research-status Report
  • [Presentation] HCV感染による慢性肝炎の病態形成と炎症性サイトカインの関与

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] Recombinant vaccinia virus encoding hepatitis C virus nonstructural protein modulates host immune response and ameliorates chronic hepatitis in mouse model

    • Author(s)
      Kiminori Kimura, Michinori Kohara
    • Organizer
      AASLD
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2011 Research-status Report
  • [Presentation] C型肝炎発症におけるウイルス蛋白質と炎症性サイトカイン

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本癌学会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] HCV持続発現マウスを用いたHCVワクチンの開発

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本肝臓学会大会
    • Place of Presentation
      福岡
    • Related Report
      2011 Research-status Report
  • [Presentation] C型慢性肝炎に対するHCV遺伝子組換えワクチニアウイルスによる治療効果

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本免疫学会学術総会
    • Place of Presentation
      千葉
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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