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Development of DNA vaccine for Clostridium difficile infection

Research Project

Project/Area Number 16K19132
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Senoh Mitsutoshi  国立感染症研究所, 細菌第二部, 主任研究官 (20646624)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsClostridium difficile / Clostridioides difficile / CDI / DNAワクチン / 毒素 / ワクチン
Outline of Final Research Achievements

Clostridioides (Clostridium) difficile infection (CDI) is a global health concern because of the high recurrence rate after standard antibiotic therapy. As serious intestinal conditions occur by C. difficile toxins, we considered measures about inactivation of toxins. Vaccination is one of prevention measures by which low recurrence rate is expected. In this study, DNA vaccine for C. difficile toxin B devoid of toxic active site was synthesized and inserted to pVAX1 to construct DNA vaccine. DNA vaccine thus prepared was transfected to HEK293T cells, and the expression of the target proteins were confirmed by western blot. Immunized mice by DNA vaccine produced anti-C. difficile toxin B antibodies and these antibodies neutralized cytotoxic activity of toxin B. Interestingly, immunized mice by DNA vaccine protected cytotoxic activity of toxin A in spite of DNA vaccine for toxin B. These results show the potential of DNA vaccine which constructed in this study as a vaccine for CDI.

Academic Significance and Societal Importance of the Research Achievements

Clostridioides (Clostridium) difficile感染症(CDI)の新たな予防法として、毒素を標的としたDNAワクチンを構築した。毒素を標的としたワクチンはトキソイドが有名であるが、毒素活性の残存や復帰の可能性がある。しかし、本研究で構築したDNAワクチンは毒素の活性領域を完全に取り除いているため、トキソイドのような副反応は起こらない。さらに、本ワクチンはC. difficileの主要な毒素であるtoxin Bとtoxin Aのどちらにも効果があるため、非常に高い効果が期待される。よって、コントロールすることが難しいCDIに対する有用な手法の1つになると考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results)

  • [Journal Article] Development of vaccine for Clostridium difficile infection using membrane fraction of nontoxigenic Clostridium difficile2018

    • Author(s)
      Senoh Mitsutoshi、Iwaki Masaaki、Yamamoto Akihiko、Kato Haru、Fukuda Tadashi、Shibayama Keigo
    • Journal Title

      Microbial Pathogenesis

      Volume: 123 Pages: 42-46

    • DOI

      10.1016/j.micpath.2018.06.039

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Clostridium difficile感染症に対するDNAワクチンの開発2018

    • Author(s)
      妹尾充敏、加藤はる、柴山恵吾
    • Organizer
      第92回日本感染症学会学術講演会第66回日本化学療法学会総会合同学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of DNA vaccine for Clostridium difficile infection2018

    • Author(s)
      妹尾充敏, 加藤はる, 岩城正昭, 柴山恵吾
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Clostridium difficile感染症(CDI)ワクチンの開発2017

    • Author(s)
      妹尾充敏
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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