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Development of novel recombinant BCG vaccine and its immunological analysis

Research Project

Project/Area Number 17K10035
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionNihon University

Principal Investigator

HONDA Mitsuo  日本大学, 医学部, 研究員 (20117378)

Co-Investigator(Kenkyū-buntansha) 相澤 志保子  日本大学, 医学部, 准教授 (30513858)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords結核 / BCG / 細胞性免疫 / ワクチン / 抗酸菌 / 組換えBCG / CTL / 感染免疫
Outline of Final Research Achievements

We developed a new recombinant BCG (rBCG) based vaccine encoding the Ag85B protein of M. tuberculosis , termed rBCG-Mbov85B. Western bloc analysis of rBCG-Mbov85B lysates showed 1.8 times higher expression of an Antigen 85B than parental BCG lysates. BCG or rBCG-Mbos85B immunization significantly reduced bacterial load in lungs and spleen compared with naive animals.
We also developed another new recombinant BCG, which expressed GFP, termed rBCG-GFP, to observe the phagocytosis of immune cells. We challenged the rBCG-GFP to THP-1, then observed the intracellular dynamics of rBCG-GFP. The intracellular rBCG-GFP could be detected at least for 48 hours. The proliferation or sterilization of rBCG-GFP could not observed during our observation.

Academic Significance and Societal Importance of the Research Achievements

結核は世界3大感染症の一つであり、地球上で最も多くの人類が感染している感染症である。100年近くBCGが結核のワクチンとして使用されてきたが、その効果は限定的である。結核は空気感染するため、感染防御のゴールドスタンダードとしてのワクチンは非常に重要である。本研究において、現行のBCGよりも効果が期待できる新たな組換えBCG (rBCG-Mbov85B)を開発することができた。また、GFPを発現するBCG(rBCG-GFP)はBCGによる免疫誘導メカニズムを詳細を検討する上で有効なツールとなりうる。日本を含め、世界的な結核罹患率を減少させるために、結核に対する免疫の理解を進めることは重要である。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results)

  • [Journal Article] MHC-restricted Ag85B-specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice2019

    • Author(s)
      Komine-Aizawa S, Jiang J, Mizuno S, Hayakawa S, Matsuo K, Boyd LF, Margulies DH, Honda M.
    • Journal Title

      .Eur J Immunol.

      Volume: 49 Issue: 9 Pages: 1399-1414

    • DOI

      10.1002/eji.201847988

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Recombinant BCG over-expressed Mycobacterium antigens enhanced Ag85B-specific CD8+ T cells.2019

    • Author(s)
      Shihoko Komine-Aizawa, Satoru Mizuno, Satoshi Hayakawa, Kazuhiro Matsuo, Mitsuo Honda
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 組換えBCGワクチンによる抗酸菌特異的免疫の誘導と結核防御効果2018

    • Author(s)
      相澤(小峯)志保子、Jiansheng Jiang、松尾和浩、Lisa F. Boyd、David H. Margulies、本多三男
    • Organizer
      第88回実験結核研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 組換えBCGワクチンによる抗酸菌特異的免疫効果誘導2018

    • Author(s)
      相澤(小峯)志保子、早川 智、本多三男
    • Organizer
      第3回抗酸菌研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Induction of antigen 85B-specific CD8+ T cells by recombinant BCG protects against mycobacterial infection2018

    • Author(s)
      Shihoko Komine-Aizawa, Satoru Mizuno, Satoshi Hayakawa, Kazuhiro Mizuno, Mitsuo Honda
    • Organizer
      第47回日本免疫学会総会・学術集会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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