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Efficacy of adjuvant for new mucosal tuberculosis booster vaccine and its mechanisms

Research Project

Project/Area Number 25460558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionNational Institute of Infectious Diseases

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)

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)
Research Collaborator Isaka Masanori  
Project Period (FY) 2013-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
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
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.

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。

Report

(7 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (25 results)

All 2019 2018 2017 2016 2015 2014 2013

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (21 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] The YvqE two-component system controls biofilm formation and acid production in Streptococcus pyogenes2016

    • Author(s)
      Isaka M, Tatsuno I, Maeyama J, Matsui H, Zhang Y, Hasegawa T
    • Journal Title

      APMIS

      Volume: In press Issue: 7 Pages: 574-85

    • DOI

      10.1111/apm.12538

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] CpG oligodeoxynucleotides as mucosal adjuvants2015

    • Author(s)
      Iho S, Maeyama J, Suzuki F
    • Journal Title

      Human Vaccines & Immunotherapeutics

      Volume: 11 Issue: 3 Pages: 755-760

    • DOI

      10.1080/21645515.2014.1004033

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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
    • Journal Title

      Plos One

      Volume: 9巻 Issue: 2 Pages: e88846-e88846

    • DOI

      10.1371/journal.pone.0088846

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Immun Ageing

      Volume: 10 Issue: 1 Pages: 25-25

    • DOI

      10.1186/1742-4933-10-25

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Mycobacterium bovis BCG Tokyo 172 sub-type間での酸化ストレス応答の差違の解析2019

    • Author(s)
      瀧井猛将、宮竹佑治、谷口恵一、伊藤佐生智、大原直也、前山順一、林 大介、山本三郎、肥田重明、小野崎菊夫
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A novel phosphodiester backbone oligodeoxynucleotide promotes vaccine ability to tuberculosis and flu2018

    • Author(s)
      Jun-ichi Maeyama, Hideki Asanuma, Daisuke Hayashi, Fumiko Suzuki, Yuriko Ozeki, Matsumoto Sohkichi, Sumiko Iho, Saburo Yamamoto
    • Organizer
      12th Vaccine Congress,
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phosphodiester-linked new oligodeoxynucleotide promotes vaccine ability to tuberculosis2018

    • Author(s)
      Jun-ichi Maeyama, Daisuke Hayashi, Toshiko Yamamoto, Toshio Yamazaki, Fumiko Suzuki, Yuriko Ozeki, Matsumoto Sohkichi, Sumiko Iho, Saburo Yamamoto
    • Organizer
      The U.S.-Japan Cooperative Medical Sciences Program, 52nd Mycobacteria Panel Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [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
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] カニクイザルを用いたMDP1とG9.1からなる結核ブースターワクチン候補の有効性評価2018

    • Author(s)
      前山順一、林大介、山本十糸子、向井徹、岡林佐知、田村敏生、山崎利雄、尾関百合子、松本壮吉、伊保澄子、山本三郎
    • Organizer
      第91回日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 遅延型過敏反応から検討した MDP1 および G9.1 からなる結核ブースターワクチン候補の免疫条件2017

    • Author(s)
      前山 順一、山崎 利雄、林 大介、山本 十糸子、尾関百合子、鈴木 史子、山口 雄大、松本 壮吉、伊保 澄子、山本 三郎
    • Organizer
      第90回日本細菌学会総会
    • Place of Presentation
      仙台市
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
  • [Presentation] Enhancement of protective mucosal immunity against influenza virus infection by a combination of Influenza antigen plus G9.1 (CpG ODN) as nasal adjuvant2017

    • Author(s)
      Hideki Asanuma, Koichiro Tateishi, Hideki Hasegawa, Norio Yamamoto, Kayoko Sato, Jun-ichi Maeyama, Sumiko Iho, Saburo Yamamoto, Takato Odagiri, Kohtaro Fujihashi
    • Organizer
      International Congress on Mucosal Immunology 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Study of a novel CpG oligodeoxynucleotide to promote vaccine ability against TB or Flu2017

    • Author(s)
      Jun-ichi Maeyama, Fumiko Suzuki, Yuriko Ozeki, Hideki Asanuma, Matsumoto Sohkichi, Sumiko Iho, Saburo Yamamoto
    • Organizer
      The 2017 International Society for Vaccines Annual Congress
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2つの感染モデルを用いたCpG-ODN G9.1添加経鼻インフルエンザワクチンの有効性2017

    • Author(s)
      立石恒一郎、山本典生、佐藤佳代子、長谷川秀樹、前山順一、伊保澄子、山本三郎、小田切孝人、藤橋浩太郎、浅沼秀樹
    • Organizer
      第21回日本ワクチン学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 新規結核菌抗原MDP1とCpG ODN G9.1アジュバントからなる結核ブースターワクチンのカニクイザルに対する有効性の検討2017

    • Author(s)
      山本三郎、林大介、山本十糸子、小山明、前山順一、網康至、須崎百合子、向井徹、岡林佐知、田村敏生、山崎利雄、松本壮吉、尾関百合子、伊保澄子、後藤義孝
    • Organizer
      第21回日本ワクチン学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Essential roles for protective SIgA Abs induced by nasal G9.1 combined influenza VLP vaccine2017

    • Author(s)
      Hideki Asanuma, Koichiro Tateishi, Kayoko Sato, Hideki Hasegawa, Jun-ichi Maeyama, Sumiko Iho, Saburo Yamamoto, Kohtaro Fujihashi, Norio Yamamoto
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 形質細胞様樹状細胞を標的とするTLR9 リガンド G9.1のアジュバントとしての作用メカニズム2016

    • Author(s)
      鈴木史子、岩崎博道、前山順一、 松本壮吉、山本三郎、伊保澄子
    • Organizer
      第20回日本ワクチン学会
    • Place of Presentation
      東京都
    • Year and Date
      2016-10-22
    • Related Report
      2016 Research-status Report
  • [Presentation] 組換え結核菌抗原MDP1およびDNAアジュバントG9.1からなる結核ブースターワクチン候補の最適化の試み2016

    • Author(s)
      前山順一、山崎利雄、山本十糸子、林大介、鈴木史子、尾関百合子、松本壮吉、伊保澄子、山本三郎
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2016-03-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Discovery of CpG-DNA and Research on Novel TB Vaccine Candidate Development2016

    • Author(s)
      Yamamoto S, Yamamoto T, Hayashi D, Iho S, Matsumoto S, Maeyama J
    • Organizer
      US-Japan Cooperative Medical Science Program 50th Anniversary TB, Leprosy Panel Meeting
    • Place of Presentation
      Bethesda, MD, USA
    • Year and Date
      2016-01-13
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development and evaluation of new tuberculosis booster vaccine candidates2015

    • Author(s)
      MAEYAMA J, HAYASHI D, SUZUKI F, OZEKI Y, MATSUMOTO S, YAMAMOTO S
    • Organizer
      第44回日本免疫学会総会・学術集会
    • Place of Presentation
      札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 結核菌組換えタンパク質MDP1およびCpG-DNAであるG9.1を用いた結核ブースターワクチンの開発2015

    • Author(s)
      前山順一、山崎利雄、山本十糸子、林大介、松本壮吉、伊保澄子、山本三郎
    • Organizer
      第88回日本細菌学会総会
    • Place of Presentation
      岐阜市
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] A novel phosphodiester oligodeoxynucleotide containing palindromic CpG motif as a mucosal adjuvant stimulates plasmacytoid dendritic cell-mediated Th1 Immunity2014

    • Author(s)
      Maeyama J, Suzuki F, Yamamoto S, Iho S
    • Organizer
      第43回日本免疫学会総会・学術集会
    • Place of Presentation
      京都市
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] TLR9リガンドであるG9.1をアジュバントとして用いた結核ブースターワクチンの開発2014

    • Author(s)
      前山順一、山崎利雄、山本十糸子、林大介、松本壮吉、伊保澄子、山本三郎
    • Organizer
      第18回日本ワクチン学会学術集会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 結核菌組換えタンパク質およびTLR9リガンドを用いた結核ブースターワクチンの結核菌噴霧感染による評価2014

    • Author(s)
      前山順一、山崎利雄、山本十糸子、 林大介、松本壮吉、網康至、須崎百合子、伊保澄子、山本三郎
    • Organizer
      第87回日本細菌学会総会
    • Place of Presentation
      東京、タワーホール船堀
    • Related Report
      2013 Research-status Report
  • [Presentation] 結核ブースターワクチンとしての結核菌組換えタンパク質MDP1およびTLR9リガンドG9.1アジュバントの結核菌噴霧感染による評価2013

    • Author(s)
      前山順一、山崎利雄、山本十糸子、林大介、松本壮吉、網康至、伊保澄子、山本三郎
    • Organizer
      第17回日本ワクチン学会学術集会
    • Place of Presentation
      津市、三重県総合文化センター
    • Related Report
      2013 Research-status Report
  • [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
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2020-03-30  

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