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Development of oral vaccine platform using lactic acid bacteria

Research Project

Project/Area Number 16K19127
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Bacteriology (including mycology)
Research InstitutionGifu Pharmaceutical University

Principal Investigator

Takahashi Keita  岐阜薬科大学, 薬学部, 助教 (50634929)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsワクチン / 粘膜ワクチン / 経口ワクチン / DNAワクチン / 腸管出血性大腸菌 / Citrobacter rodentium / 乳酸菌 / M細胞 / 粘膜ワクチン系 / パイエル板 / アジュバント / 粘膜免疫 / 分泌型IgA / 細胞性免疫
Outline of Final Research Achievements

In this study, we developed a novel oral vaccine system using lactic acid bacteria as a carrier of vaccine and obtained the following results. 1) We demonstrated that oral administration of lactic acid bacteria-expressing model antigen can induce antigen-specific immunity in mice. Furthermore, targeting to M cells, specialized intestinal epithelial cells for luminal antigen uptake to Peyer’s patches, can enhance the ability of antigen expressing lactic acid bacteria to induce antigen-specific immunity. 2) We revealed the mechanism of plasmid DNA delivery to host intestinal cells from orally administrated lactic acid bacteria. 3) We established an experimental system capable of evaluating the protective effect of the novel oral vaccine system, including lactic acid bacteria vaccine, using murine pathogenic C. rodentium infection model.

Academic Significance and Societal Importance of the Research Achievements

乳酸菌をキャリアとして用いることで、現行の注射型ワクチンでは誘導が難しい粘膜免疫の誘導が可能なワクチン系を実現できる可能性を示した。経口ワクチンの有効性を増強する方法として提唱されているM細胞標的化が乳酸菌ワクチン系においても有効に働くことを示すとともに、M細胞標的化の有効性を裏付ける成果を得た。本研究で確立した実験系を用いることで、これまでほとんど行われていない乳酸菌ワクチン系の有効性の比較評価が可能になった。

Report

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

    (18 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (13 results) Remarks (1 results)

  • [Int'l Joint Research] Micalis Institute, INRA(フランス)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Protective effects of oral immunization with formalin-inactivated whole-cell Citrobacter rodentium on Citrobacter rodentium infection in mice.2019

    • Author(s)
      Keita Takahashia, Yuki Hanamura, Nagisa Tokunoh, Kohei Kassai, Masaru Matsunishi, Shiori Watanabe, Tsuyoshi Sugiyama, Naoki Inoue
    • Journal Title

      Journal of Microbiological Methods

      Volume: 159 Pages: 62-68

    • DOI

      10.1016/j.mimet.2019.02.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peyer’s Patches as a Portal for DNA Delivery by <i>Lactococcus lactis</i> <i>in Vivo</i>2018

    • Author(s)
      Ayumu Yano, Keita Takahashi, Yusuke Mori, Shiori Watanabe, Yuki Hanamura, Tsuyoshi Sugiyama, Naoki Inoue
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 2 Pages: 190-197

    • DOI

      10.1248/bpb.b17-00657

    • NAID

      130006329249

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] M cell-targeting strategy enhances systemic and mucosal immune responses induced by oral administration of nuclease-producing L. lactis.2018

    • Author(s)
      Keita Takahashi, Ayumu Yano, Shiori Watanabe, Philippe Langella, Luis G. Berm&uacute;dez-Humar&aacute;n, Naoki Inoue
    • Journal Title

      Applied Microbiology and Biotechnology

      Volume: 102 Issue: 24 Pages: 10703-10711

    • DOI

      10.1007/s00253-018-9427-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] LAP increases the DNA delivery efficiency of Internalin A-expressing invasive Lactococcus lactis2019

    • Author(s)
      Nozomi Orito, Keita Takahashi, Daiki Yanagisawa, Naoki Inoue
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] M cell-targeting enhances immune responses induced by oral immunization with Ag-producing L. lactis2019

    • Author(s)
      Keita Takahashi*, Nozomi Orito, Nagisa Tokunoh, Naoki Inoue
    • Organizer
      第93回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Citrobacter rodentium由来抗原を発現する組換え乳酸菌の経口投与による免疫誘導2018

    • Author(s)
      井上直樹、花村有希、髙橋圭太、渡邊詩織、松西 優、杉山剛志
    • Organizer
      第47回東海乳酸菌研究報告会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of a Rapid and Convenient Method for Quantification of Citrobacter rodentium2018

    • Author(s)
      Yuki Hanamura, Keita Takahashi, Masaru Matsunishi, Kohei Kassai, Shiori Watanabe, Yusuke Mori, Nozomi Orito, Tsuyoshi Sugiyama, Naoki Inoue
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] M cell-targeting enhances immune responses induced by nuclease-producing Lactococcus lactis2018

    • Author(s)
      Keita Takahashi, Ayumu Yano, Shiori Watanabe, Yusuke Mori Tsuyoshi Sugiyama, Naoki Inoue
    • Organizer
      第92回日本細菌学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Citrobacter rodentium由来抗原を発現する組換え乳酸菌の経口投与による免疫誘導2018

    • Author(s)
      井上直樹、花村有希、髙橋圭太、渡邊詩織、松西 優、杉山剛志、Philippe Langella、Luis G. Berm&uacute;dez-Humar&aacute;n、Tarik Issad
    • Organizer
      第47回 東海乳酸菌研究報告会
    • Related Report
      2017 Research-status Report
  • [Presentation] Development of a rapid and convenient method for quantification of Citrobacter rodentium2018

    • Author(s)
      花村有希、高橋圭太、松西優、葛西康平、渡辺詩織、森祐介、折戸希、杉山剛志、井上直樹
    • Organizer
      第91回 日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] M cell-targeting enhances immune responses induced by nuclease-producing Lactococcus lactis2018

    • Author(s)
      高橋圭太、矢野歩、渡辺詩織、森祐介、杉山剛志、井上直樹
    • Organizer
      第91回 日本細菌学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 乳酸菌による機能性蛋白の発現と経口ワクチンへの応用2017

    • Author(s)
      髙橋圭太、森祐介、花村有希、折戸希、矢野歩、渡辺詩織、 杉山剛志、井上直樹
    • Organizer
      第8回機能性健康食品研究講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] 乳酸菌を用いた経口ワクチン系の改良2017

    • Author(s)
      森祐介、花村有希、折戸希、井上直樹、高橋圭太
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部 合同学術大会2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 組換え乳酸菌を用いた免疫誘導2017

    • Author(s)
      井上直樹、渡辺詩織、花村有希、矢野歩、松西優、森祐介、杉山剛志、高橋圭太、Philippe Langella, Luis G. Berm&uacute;dez-Humar&aacute;n, Tarik Issad
    • Organizer
      第46回 東海乳酸菌研究会
    • Place of Presentation
      愛知県
    • Related Report
      2016 Research-status Report
  • [Presentation] モデル抗原を発現する組換え乳酸菌を用いた免疫条件の検討と免疫誘導の評価2016

    • Author(s)
      渡邊 詩織、 矢野 歩、 森 祐介、 花村 有希、 高橋 圭太、杉山剛志、井上直樹、Philippe Langella, Luis G. Berm&uacute;dez-Humar&aacute;n, Tarik Issad
    • 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] 乳酸菌を用いたDNAワクチン送達法の検討2016

    • Author(s)
      矢野 歩、高橋 圭太、松西 優、渡邊 詩織、森 祐介、花村 有希、所 俊志、Langella Phillippe、Bermudez-Humaran Luis、杉山 剛志、井上 直樹
    • Organizer
      第7回 機能性健康食品(蜂産品)研究会
    • Place of Presentation
      岐阜県
    • Related Report
      2016 Research-status Report
  • [Remarks] 岐阜薬科大学 生命薬学大講座 感染制御学研究室

    • URL

      http://sv1.gifu-pu.ac.jp/lab/kansen/

    • Related Report
      2018 Annual Research Report 2017 Research-status Report 2016 Research-status Report

URL: 

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

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