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Basic research for the TB vaccine development based on the novel drug delivery system.

Research Project

Project/Area Number 17K08821
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bacteriology (including mycology)
Research InstitutionThe University of Tokyo

Principal Investigator

Nakahashi Rika  東京大学, 医科学研究所, 特任講師 (80391887)

Co-Investigator(Kenkyū-buntansha) 幸 義和  東京大学, 医科学研究所, 特任研究員 (60345030)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsカチオン化ナノゲル / 経鼻ワクチン / 粘膜免疫応答 / ドラッグデリバリーシステム / 結核ワクチン / 感染症
Outline of Final Research Achievements

We have developed the novel nasal vaccine system, a cationized nanogel consisting of polysaccharide pullulan and cholesterol, and demonstrated its effectiveness and safety in mice and monkeys using surface antigens of S. pneumoniae. In this study, we aim to develop a nasal tuberculosis vaccine using M. tuberculosis derived a several antigen candidates. In order to induce a high protective efficacy against infection, the effect on the immune response by the combination of a vaccine antigens and mucosal adjuvants is screened by detecting antigen-specific T cells (Th1) after nasal immunization in mice. In addition, the protective efficacy of the vaccine will be verified by the challenge experiment in vaccinated mice, and we aim to proceed the clinical use of the nasal tuberculosis vaccine in adults.

Academic Significance and Societal Importance of the Research Achievements

新興再興感染症である結核は、成人においては現行のBCGワクチンが無効であることから、肺炎を併発し、重症化すると死亡を含む重篤な疾病を発症させることが知られているが、成人を対象とした結核に有効なワクチンは未だ開発されていない。結核菌は、上気道から感染し下気道での肺炎を誘導するため、従来の注射型よりも粘膜面に効率よく免疫応答を惹起できる経鼻ワクチンの開発が期待されている。一方、経鼻投与ではワクチン抗原やアジュバントの脳移行などの安全性を配慮する必要もある。そこで、免疫誘導に優れ且つ中枢にも影響しないナノゲルシステムを用いた結核経鼻ワクチンは、最も実用化に近いワクチン候補として期待される。

Report

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

    (8 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] A role for the CCR5?CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization2019

    • Author(s)
      Joo Sunyi、Suwanto Aldina、Sato Ayuko、Nakahashi-Ouchida Rika、Mori Hiromi、Uchida Yohei、Sato Shintaro、Kurashima Yosuke、Yuki Yoshikazu、Fujihashi Kohtaro、Kawaguchi Yasushi、Kiyono Hiroshi
    • Journal Title

      Mucosal Immunology

      Volume: 12 Issue: 6 Pages: 1391-1403

    • DOI

      10.1038/s41385-019-0203-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ナノゲルデリバリーシステムによる肺炎球菌経鼻ワクチンの開発2019

    • Author(s)
      中橋理佳、幸義和、清野 宏
    • Journal Title

      炎症と免疫

      Volume: 27 Pages: 19-24

    • Related Report
      2018 Research-status Report
  • [Journal Article] Nanogel-based nasal vaccines for infectious and lifestyle-related diseases.2019

    • Author(s)
      Azegami T, Yuki Y, Nakahashi R, Itoh H, Kiyono H.
    • Journal Title

      Molecular Immunology

      Volume: 98 Pages: 19-24

    • DOI

      10.1016/j.molimm.2017.10.022

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cationic pullulan nanogel as a safe and effective nasal vaccine delivery system for respiratory infectious diseases.2018

    • Author(s)
      Nakahashi-Ouchida R., Yuki Y., Kiyono H.
    • Journal Title

      Human Vaccines & Immunotherapeutics

      Volume: 14 Issue: 12 Pages: 2189-2193

    • DOI

      10.1080/14760584.2017.1395702

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 粘膜ワクチンの潮流と課題2018

    • Author(s)
      西村 潤、中橋 理佳、幸 義和、清野 宏
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 18227-18234

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 肺炎球菌表層タンパク質2020

    • Inventor(s)
      幸義和・中橋理佳・清野宏
    • Industrial Property Rights Holder
      幸義和・中橋理佳・清野宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞性免疫を誘導する経鼻ワクチン2019

    • Inventor(s)
      幸義和・中橋理佳・清野宏
    • Industrial Property Rights Holder
      幸義和・中橋理佳・清野宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞性免疫を誘導する経鼻ワクチン2018

    • Inventor(s)
      清野 宏、中橋 理佳、幸 義和
    • Industrial Property Rights Holder
      清野 宏、中橋 理佳、幸 義和
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-014651
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2025-03-27  

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