Study of tuberculosis and development of vaccine in latent infected cynomolgus monkeys.
| Project/Area Number |
17H04079
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
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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)
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| 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(24 results)
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[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.
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Journal Title
Parasitology International.
Volume: 76
Pages: 102034-102034
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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
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Journal Title
Experimental Animals
Volume: 69
Issue: 1
Pages: 18-25
DOI
NAID
ISSN
0007-5124, 1341-1357, 1881-7122
Related Report
Peer Reviewed / Int'l Joint Research
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[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,
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Journal Title
Immunity
Volume: 50
Issue: 5
Pages: 1305-1316
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[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.
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Journal Title
Int Immunol
Volume: 30
Issue: 10
Pages: 471-481
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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