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Study of tuberculosis and development of vaccine in latent infected cynomolgus monkeys.

Research Project

Project/Area Number 17H04079
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

Yasutomi Yasuhiro  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 霊長類医科学研究センター, センター長 (90281724)

Co-Investigator(Kenkyū-buntansha) 辻村 祐佑  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 霊長類医科学研究センター, 研究員 (30512404)
山本 拓也  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, プロジェクトリーダー (60752368)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords結核 / ワクチン / 潜伏感染 / カニクイザル / 感染防御 / 組み換えウイルス / 感染症 / 免疫学 / 細菌 / ウイルス
Outline of Final Research Achievements

It was confirmed that the cynomolgus monkeys inoculated with Mycobacterium Erdman tuberculosis strain at 10 CFU by respiratory tract became latently infected at 9/10. These latently infected cynomolgus monkeys showed no more than the chest image by CT, and showed a positive reaction in IGRA in the early stage of infection, but after that, they moved to ± (false positive), and they did not show more than remarkable.
When healthy cynomolgus monkeys were immunized with rHPIV2-EM1 and rHPIV2-Ag85B by intranasal administration, and then pathogenic M. tuberculosis was inoculated, a protective effect in the lung was found to be superior to the BCG vaccine. In addition, a very strong M. tuberculosis-specific immune response was induced in the latently infected M. tuberculosis individuals.

Academic Significance and Societal Importance of the Research Achievements

結核は世界中で蔓延し、800万人以上の新規患者、100万人以上の死亡者が報告されている。結核菌は宿主の体内環境に適応し長期に潜伏感染する細胞内寄生細菌である。世界保健機関 (WHO) の報告では人類の30%が結核菌に感染していると述べられており、そのうちの5~10%が感染後2年以内に活動性結核を発症するが大半は非発症のままである。これらのことから、潜伏期の結核の発症を防御するような予防ワクチンや治療薬、発症に至る詳細な解析や診断マーカーの検討は極めて有意義であり、本申請研究ではカニクイザルを用いて詳細な検討を行い、ヒトへの応用に近い研究であると考えられる。

Report

(3 results)
  • 2019 Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report

Research Products

(6 results)

All 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] OCS1 antagonist-expressing recombinant BCG enhances anti-tuberculosis protection in a mouse model2019

    • Author(s)
      Mizuno S, Soma S, Inada H, Kanuma T, Matsuo K, Yasutomi Y.
    • Journal Title

      J. Immunol

      Volume: 203

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] STING agonists activate latently infected cells and enhance SIV-specific responses ex vivo in naturally SIV controlled cynomolgus macaques2019

    • Author(s)
      Yamamoto Takuya、Kanuma Tomohiro、Takahama Shokichi、Okamura Tomotaka、Moriishi Eiko、Ishii Ken J.、Terahara Kazutaka、Yasutomi Yasuhiro
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-019-42253-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary Role of Suppressor of Cytokine Signaling 1 in Mycobacterium bovis BCG Infection.2018

    • Author(s)
      Soma S, Kawai S, Inada H, Watanabe K, Mizuno S, Kato S, Matsuo K, Yasutomi Y.
    • Journal Title

      Infect Immun.

      Volume: 86(11) Issue: 11 Pages: 471-480

    • DOI

      10.1128/iai.00376-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunological association of inducible bronchus-associated lymphoid tissue organogenesis in Ag85B-rHPIV2 vaccine-induced anti-tuberculosis mucosal immune responses in mice.2018

    • Author(s)
      Nagatake T, Suzuki H, Hirata S, Matsumoto N, Wada Y, Morimoto S, Nasu A, Shimojou M, Kawano M, Ogami K, Tsujimura Y, Kuroda E, Iijima N, Hosomi K, Ishii KJ, Nosaka T, Yasutomi Y, Kunisawa J.
    • Journal Title

      Int Immunol

      Volume: 30 Issue: 10 Pages: 471-481

    • DOI

      10.1093/intimm/dxy046

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 粘膜免疫誘導型新規結核ワクチンの開発2018

    • Author(s)
      保富康宏
    • Organizer
      日本結核病学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Recombinant BCG expressing SOCS1 antagonist as a novel TB vaccine2018

    • Author(s)
      Yasuhiro Yasutomi
    • Organizer
      rd World Congress and Expo on Immunology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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

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