Efficacy of adjuvant for new mucosal tuberculosis booster vaccine and its mechanisms
| Project/Area Number |
25460558
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Maeyama Jun-ichi 国立感染症研究所, 血液・安全性研究部, 主任研究官 (40199641)
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| Co-Investigator(Kenkyū-buntansha) |
伊保 澄子 新潟大学, 医歯学総合研究科, 客員研究員 (80151653)
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| Research Collaborator |
Isaka Masanori
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| Project Period (FY) |
2013-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アジュバント / ワクチン / 粘膜免疫 / 結核 / CpG / 感染防御 / CpG-ODN / 形質細胞様樹状細胞 / インターフェロンアルファ / 遅延型過敏反応 / CpG-オリゴDNA / インターフェロンα / CpG-DNA / 抗体 / 粘膜 / Th1 |
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| Outline of Final Research Achievements |
When G9.1, which is a novel oligo DNA containing CpG motif, was nasally administered as a mucosal adjuvant with diphtheria toxoid, enhancement of the specific antibody production and that of the diphtheria antitoxin titers were observed. Involvement of TLR9 and plasmacytoid dendritic cells (pDC) in adjuvanticity of G9.1 was confirmed. Coculture of mouse bone marrow cells with G9.1 strongly induced IFN-αproduction. T-bet, which is a specific transcription factor for Th1 cells, was strongly expressed. Therefore, G9.1 was shown to be a mucosal adjuvant that enhances Th1 immunity via TLR9 of pDC. And, also, IFN-α produced by pDC near the mucosal membrane is an important factor as mechanisms of adjuvanticity of G9.1.
The evaluation system of tuberculosis booster vaccine efficacy by delayed type hypersensitivity reaction against tuberculosis antigen was established by guinea pigs administered BCG with low immunostimulatory ability as prime immunization.
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| Academic Significance and Societal Importance of the Research Achievements |
粘膜アジュバントG9.1の作用機構の解明を目指すことで粘膜免疫増強機構の一端を明らかにすることによって、粘膜ワクチンによる投与法の改良・簡素化・経済性からの接種率の向上も期待でき、国民の健康のみならず国際的にも貢献が期待できる。
結核防御免疫の評価系確立は、結核ワクチンの開発を促進することが期待できる。ブースターワクチンが人への適用に至れば、BCG初回免疫による結核免疫の増強を図ることができる。成人肺結核の予防対策に対して、結核の中蔓延国である日本国民の健康のみならず、発展途上国など国際的にも貢献ができる。
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Report
(7 results)
Research Products
(25 results)
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[Journal Article] A palindromic CpG-containing phosphodiester oligodeoxynucleotides as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated TH1 immunity2014
Author(s)
Maeyama JI, Takatsuka H, Suzuki F, Kubota A, Horiguchi S, Komiya T, Shimada I, Murata E, Osawa Y, Kitagawa H, Matsuki T, Yamamoto S, Iho S
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Journal Title
Plos One
Volume: 9巻
Issue: 2
Pages: e88846-e88846
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reactivation of immune responses against Mycobacterium tuberculosis by boosting with the CpG oligomer in aged mice primarily vaccinated with Mycobacterium bovis BCG2013
Author(s)
Taniguchi K, Takii T, Yamamoto S, Maeyama J, Iho S, Maruyama M, Iizuka N, Ozeki Y, Matsumoto S, Hasegawa T, Miyatake Y, Itoh S, Onozaki K.
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Journal Title
Immun Ageing
Volume: 10
Issue: 1
Pages: 25-25
DOI
Related Report
Peer Reviewed
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[Presentation] The effects of the booster vaccine composed of MDP1 and G9.1 against tuberculosis in cynomolgus monkeys2018
Author(s)
Daisuke Hayashi, Jun-ichi Maeyama, Toshiko Yamamoto, Toshio Yamazaki, Tetsu Mukai, Toshiki Tamura, Sachi Okabayashi, Fumiko Suzuki, Yuriko Ozeki, Akira Yokoyama, Yuriko Suzaki, Yasushi Ami, Yoshitaka Goto, Sumiko Iho, Sohkichi Matsumoto, Saburo Yamamoto
Organizer
The U.S.-Japan Cooperative Medical Sciences Program, 52nd Mycobacteria Panel Meeting
Related Report
Int'l Joint Research
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[Presentation] Boosting effect of Oligo B in super aged mice primarily vaccinated with Mycobacterium bovis BCG on the protection activity against Mycobacterium tuberculosis infection2013
Author(s)
Takii T, Taniguchi K, Yamamoto S, Maeyama J, Iho S, Maruyama M, Iizuka N, Ozeki Y, Matsumoto S, Itoh S, Onozaki K
Organizer
From Range Mycobacteria Conference
Place of Presentation
コロラド、USA
Related Report
