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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

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

    (24 results)

All 2020 2019 2018

All Journal Article (18 results) (of which Int'l Joint Research: 15 results,  Peer Reviewed: 18 results,  Open Access: 11 results) Presentation (5 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] Echocardiographic evaluation of cardiac function in cynomolgus monkeys over a wide age range.2020

    • Author(s)
      Nakayama S, Koie H, Pai C, Ito-Fujishiro Y, Kanayama K, Sankai T, Yasutomi Y, Ageyama N.
    • Journal Title

      Exp Anim

      Volume: - Issue: 3 Pages: 336-344

    • DOI

      10.1538/expanim.19-0128

    • NAID

      130007884751

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of an effective alternative model for in vivo hypnozoite-induced relapse infections: a Japanese macaque (Macaca fuscata) model experimentally infected with Plasmodium cynomolgi2020

    • Author(s)
      Kawai S, Annoura T, Araki T, Shiogama Y, Shogo S, Sato MO, Kaneko O, Yasutomi Y, Chigusa Y.
    • Journal Title

      Parasitology International

      Volume: 76 Pages: 102096-102096

    • DOI

      10.1016/j.parint.2020.102096

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis2020

    • Author(s)
      Fujimoto Minoru、Matsumoto Tomoshige、Serada Satoshi、Tsujimura Yusuke、Hashimoto Shoji、Yasutomi Yasuhiro、Naka Tetsuji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 3384-3384

    • DOI

      10.1038/s41598-020-60450-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional electron microscopy analysis reveals endopolygeny-like nuclear architecture segregation in Plasmodium oocyst development.2020

    • Author(s)
      ARAKI T, KAWAI S, KAKUTA S, KOBAYASHI H, UMEKI Y, SAITO-NAKANO Y, SASAKI T, NAGAMUNE K, YASUTOMI Y, NOZAKI T, FRANKE-FAYARD B, KHAN SM, HISAEDA H, ANNOUNRA T.
    • Journal Title

      Parasitology International.

      Volume: 76 Pages: 102034-102034

    • DOI

      10.1016/j.parint.2019.102034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Establishment of a new formula for QT interval correction using a large colony of cynomolgus monkeys2020

    • Author(s)
      Nakayama S, Koie H, Kato-Tateishi M, Pai C, Ito-Fujishiro Y, Kanayama K, Sankai T, Yasutomi Y, Ageyama N
    • Journal Title

      Experimental Animals

      Volume: 69 Issue: 1 Pages: 18-25

    • DOI

      10.1538/expanim.19-0009

    • NAID

      130007791581

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Successful Inflammation Imaging of Non-Human Primate Hearts Using an Antibody Specific for Tenascin-C2019

    • Author(s)
      Ageyama N., Kurosawa H., Fujimoto O., Uehara T., Hiroe M., Arano Y., Yoshida T., Yasutomi Y., Imanaka-Yoshida K
    • Journal Title

      International Heart Journal

      Volume: 60 Issue: 1 Pages: 151-158

    • DOI

      10.1536/ihj.17-734

    • NAID

      130007557133

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2019-01-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response2019

    • Author(s)
      Sanada Takahiro、Yamamoto Naoki、Kayesh Mohammad Enamul Hoque、Tsukiyama-Kohara Kyoko、Hasegawa Hideki、Miyazaki Takashi、Takano Jun-ichiro、Shiogama Yumiko、Yasutomi Yasuhiro、Goh Yasumasa、Yoshida Osamu、Hiasa Yoichi、Kohara Michinori
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 520 Issue: 1 Pages: 86-92

    • DOI

      10.1016/j.bbrc.2019.09.072

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Construction of complete Tupaia belangeri transcriptome database by whole-genome and comprehensive RNA sequencing2019

    • Author(s)
      Sanada Takahiro、Tsukiyama-Kohara Kyoko、Shin-I Tadasu、Yamamoto Naoki、Kayesh Mohammad Enamul Hoque、Yamane Daisuke、Takano Jun-ichiro、Shiogama Yumiko、Yasutomi Yasuhiro、Ikeo Kazuho、Gojobori Takashi、Mizokami Masashi、Kohara Michinori
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 12372-12372

    • DOI

      10.1038/s41598-019-48867-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunization with components of the viral fusion apparatus elicits antibodies that neutralize Epstein-Barr virus in B cells and epithelial cells.2019

    • Author(s)
      Bu W, Joyce MG, Nguyen H, Banh DV, Aguilar F, Tariq Z, Yap ML, Tsujimura Y, Gillespie RA, Tsybovsky Y, Andrews SF, Narpala SR, McDermott AB, Rossmann MG, Yasutomi Y, Nabel GJ, Kanekiyo M, Cohen JI,
    • Journal Title

      Immunity

      Volume: 50 Issue: 5 Pages: 1305-1316

    • DOI

      10.1016/j.immuni.2019.03.010

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Avian H5N1 influenza virus infection causes severe pneumonia in the Northern tree shrew (Tupaia belangeri)2019

    • Author(s)
      Takahiro Sanada, Fumihiko Yasui, Tomoko Honda, Mohammad Enamul Hoque Kayesh, Jun-ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Kyoko Tsukiyama-Kohara, and Michinori Kohara
    • Journal Title

      Virology

      Volume: 529 Pages: 101-110

    • DOI

      10.1016/j.virol.2019.01.015

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elevated Membrane Cholesterol Disrupts Lysosomal Degradation to Induce β-Amyloid Accumulation2019

    • Author(s)
      Takeuchi Shingo、Ueda Naoya、Suzuki Keiko、Shimozawa Nobuhiro、Yasutomi Yasuhiro、Kimura Nobuyuki
    • Journal Title

      The American Journal of Pathology

      Volume: 189 Issue: 2 Pages: 391-404

    • DOI

      10.1016/j.ajpath.2018.10.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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] Partial Deletion of Glycoprotein B5R Enhances Vaccinia Virus Neutralization Escape while Preserving Oncolytic Function2019

    • Author(s)
      Nakatake Motomu、Kurosaki Hajime、Kuwano Nozomi、Horita Kosuke、Ito Mai、Kono Hiromichi、Okamura Tomotaka、Hasegawa Kosei、Yasutomi Yasuhiro、Nakamura Takafumi
    • Journal Title

      Molecular Therapy - Oncolytics

      Volume: 14 Pages: 159-171

    • DOI

      10.1016/j.omto.2019.05.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] 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
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] SOCS1 antagonist-expressing recombinant BCG enhances anti-tuberculosis protection in a mouse model.2019

    • Author(s)
      Yasuhiro Yasutomi
    • Organizer
      103rd Immunology 2019, American Association of Immunology,
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Essential role of primate in vaccine development in Japan.2019

    • Author(s)
      Yasuhiro Yasutomi
    • Organizer
      13th Vaccine congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Hepatitis E virus vaccine.2019

    • Author(s)
      Yasuhiro Yasutomi
    • Organizer
      7th National Virology Conference Mongolia
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [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
  • [Book] Mucosal Vaccine2019

    • Author(s)
      Tsujimura Y, Yasutomi Y.
    • Total Pages
      450
    • Publisher
      ELSEVIER
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2023-12-25  

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