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Development of novel tuberculosis vaccine mainly targeting to humoral immunity

Research Project

Project/Area Number 16K09584
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionOsaka City University

Principal Investigator

Niki Mamiko  大阪市立大学, 大学院医学研究科, 講師 (20438229)

Co-Investigator(Kenkyū-buntansha) 星野 仁彦  国立感染症研究所, ハンセン病研究センター 感染制御部, 室長 (20569694)
Research Collaborator OOTA Ken  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords結核 / 液性免疫 / ワクチン / 感染症
Outline of Final Research Achievements

A novel tuberculosis vaccine to replace BCG has long been desired. Although cellular mediated immunity has been thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb), increasing evidences suggest that humoral immunity might also play an important role in the protection of Mtb infection.
To evaluate the role of humoral immunity against Mtb, we compared immunoglobulin titers against Mtb antigens to clinical and immunological parameters. We observed the IgA titers against Mtb antigens were significantly correlated with clinical status, including serum concentration of C reactive protein (CRP), suggesting that specific IgA antibodies protect the promotion of Mtb. We also found that changes in CRP during treatment were associated with high levels of specific IgA avidities to mycobacterial antigens. These observations lead to postulate the induction of humoral immunity should be included as an option in TB vaccine development strategies.

Academic Significance and Societal Importance of the Research Achievements

抗結核ワクチンとして現在用いられているものはBCGのみであるが、成人の肺結核に対してはその予防効果は疑問視されている。肺炎球菌などの経気道感染を起こす病原体については、粘膜上で誘導される分泌型IgAを主体としたワクチン開発が盛んに行われていることから、ワクチンによる気道粘膜における結核菌抗原特異的IgAの誘導は感染防御において高い効果を発揮すると考えられる。本研究では、活動期および休眠期の結核菌抗原に対する治療前および治療後の患者血清中特異抗体を測定し、臨床マーカーとの比較を行うことにより、感染防御および炎症抑制に働く液性粘液を誘導する抗原の同定につながることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Longitudinal Evaluation of Humoral Immunity and Bacterial and Clinical Parameters Reveals That Antigen-Specific Antibodies Suppress Inflammatory Responses in Active Tuberculosis Patients2018

    • Author(s)
      Niki Mamiko、Yoshiyama Takashi、Miyamoto Yuji、Okumura Masao、Niki Makoto、Oinuma Ken-ichi、Kaneko Yukihiro、Matsumoto Sohkichi、Sasaki Yuka、Ogata Hideo、Goto Hajime、Kudoh Shoji、Hoshino Yoshihiko
    • Journal Title

      Journal of Immunology Research

      Volume: 2018 Pages: 1-11

    • DOI

      10.1155/2018/4928757

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages.2018

    • Author(s)
      Inoue M, Niki M, Ozeki Y, Nagi S, Chadeka EA, Yamaguchi T, Osada-Oka M, Ono K, Oda T, Mwende F, Kaneko Y, Matsumoto M, Kaneko S, Ichinose Y, Njenga SM, Hamano S, Matsumoto S.
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 6736-6736

    • DOI

      10.1038/s41598-018-24233-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longitudinal evaluation of humoral immunity and bacterial and clinical parameters reveals that antigen-specific antibodies suppress inflammatory responses in active tuberculosis patients2017

    • Author(s)
      Niki M, Yoshiyama T, Miyamoto Y, Okumura M, Niki M, Oinuma K, kaneko Y, Matsumoto S, Sasaki Y, Ogata H, Gotoh H, Kudoh S, Hoshino Y
    • Journal Title

      Journal of Immunology Research

      Volume: -

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Longitudinal evaluation of humoral immunity to Mycobacterium tuberculosis-specific antigens for correlation with clinical status and effective vaccine development.2017

    • Author(s)
      Niki M, Yoshiyama T, Kaneko Y, Matsumoto S, Kudoh S, Goto H, Hoshino Y.
    • Organizer
      Keystone Symposia: New developments in our understanding of tuberculosis.
    • Place of Presentation
      Vancouver, British Columbia Canada
    • Year and Date
      2017-01-14
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 結核菌感染における液性免疫の役割2017

    • Author(s)
      仁木満美子, 星野仁彦, 仁木誠, 老沼研一, 金子幸弘
    • Organizer
      第60回日本感染症学会中日本地方会学術集会
    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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