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Evaluation of efficacy by rBCG-SOCS1DN vaccination in cynomolgus macaques

Research Project

Project/Area Number 18K15162
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

Kanuma Tomohiro  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 免疫老化プロジェクト, プロジェクト研究員 (30794044)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords結核 / BCGワクチン / カニクイザル / マクロファージ / 感染症 / 免疫学 / SOCS1 / BCG / 細胞性免疫 / サル動物モデル
Outline of Final Research Achievements

Tuberculosis is one of the largest infectious diseases in Japan. Although there is a BCG vaccine as a tuberculosis preventive vaccine, no clear preventive effect on pulmonary tuberculosis has been observed. Therefore, this study aimed to lay the foundation for the development of a new BCG vaccine that is more effective than the current BCG vaccine. We focused on the cytokine suppressor molecule (SOCS) that negatively regulates the host immune response of mycobacteria such as BCG, and constructed a BCG strain carrying a SOCS1 mutant (SOCS1DN) that acts as an antagonist of SOCS1. As a result of inoculating cynomolgus monkeys with the prepared BCG-cynoSOCS1DN as a vaccine strain, it was suggested that this vaccine is highly useful in reducing inflammation and increasing T cell response compared to the current BCG.

Academic Significance and Societal Importance of the Research Achievements

結核を予防する手段としてBCGワクチンがあるが、肺結核に対する明確な予防効果は認められていない。そういった背景から世界中で肺結核予防ワクチンの研究開発が活発に行われている。しかしながら、未だ臨床の現場では有効なワクチンは存在していない。本研究では、世界的にも安全性の高いBCG Tokyo株を用いて、BCG-cynoSOCS1DNを作製した。この株を肺結核モデル動物であるカニクイザルをモデルとして用いて検証を行った。その結果、炎症反応を軽減させ、かつ効果のあるワクチン候補株の作製に成功した。

Report

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

    (4 results)

All 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] SOCS1 Antagonist-Expressing Recombinant Bacillus Calmette-Guerin Enhances Antituberculosis Protection in a Mouse Model2019

    • Author(s)
      Mizuno Satoru、Soma Shogo、Inada Hiroyasu、Kanuma Tomohiro、Matsuo Kazuhiro、Yasutomi Yasuhiro
    • Journal Title

      The Journal of Immunology

      Volume: 203 Issue: 1 Pages: 188-197

    • DOI

      10.4049/jimmunol.1800694

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A unique nanoparticulate TLR9 agonist enables a HA split vaccine to confer FcγR-mediated protection against heterologous lethal influenza virus infection2018

    • Author(s)
      Yamamoto Takuya、Masuta Yuji、Momota Masatoshi、Kanekiyo Masaru、Kanuma Tomohiro、Takahama Shoukichi、Moriishi Eiko、Yasutomi Yasuhiro、Saito Takashi、Graham Barney S、Takahashi Yoshimasa、Ishii Ken J
    • Journal Title

      International Immunology

      Volume: 31 Issue: 2 Pages: 81-90

    • DOI

      10.1093/intimm/dxy069

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] STING ligands induce re-activation of latently SIV-infected cells and augment SIV- specific CTL responses2018

    • Author(s)
      Tomohiro Kanuma
    • Organizer
      19th Kumamoto AIDS seminar
    • Related Report
      2018 Research-status Report
  • [Presentation] STING ligands re-activate latently infected cells and enhances CTL response in PBMC from cynomolgus monkeys naturally controlling SIV.2018

    • Author(s)
      Tomohiro Kanuma
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2021-02-19  

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