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Research on oral vaccine systems using lactic acid bacteria as vectors

Research Project

Project/Area Number 19K16649
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionGifu Pharmaceutical University

Principal Investigator

TAKAHASHI Keita  岐阜薬科大学, 薬学部, 講師 (50634929)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords粘膜ワクチン / 乳酸菌 / DNAワクチン / 細菌様粒子 / Citrobacter rodentium / 経口ワクチン / 乳酸菌ベクター
Outline of Research at the Start

近年、全身性免疫(体内に侵入してきた病原体に有効な免疫)と粘膜免疫(病原体の体内への侵入を阻止する免疫)の両方を活性化できる「飲むワクチン」が注目されている。本研究は、安全かつ効率的に粘膜免疫を活性化できる組換え乳酸菌をベクターとして用いた飲むワクチン「乳酸菌ワクチン系」の開発を目指したもので、これまでの研究から明らかになってきた乳酸菌ワクチン系の課題克服を目的とした研究を行う。

Outline of Final Research Achievements

In this study, we conducted basic research related to the development of a novel oral vaccine system using lactic acid bacteria (LAB) as a vaccine carrier. The oral (or nasal) immunogenicity of three different systems, including 1) vaccine antigen-expressing LAB, 2) antigen-bound bacterium-like particles (BLP) which is composed of the cell wall peptidoglycan structure of heat-killed LAB, 3) LAB carrying plasmid DNA that functions as a DNA vaccine, was evaluated in mice. No strong immunogenicity was observed by oral administration in any of the systems, but significant immunogenicity was observed by nasal administration. Among these, the nasal administration of antigen-bound BLP induces a strongest antigen-specific immune responses not only to the systemic but also to the respiratory and the intestinal mucosa.

Academic Significance and Societal Importance of the Research Achievements

粘膜ワクチンは、粘膜組織を介して感染する病原体に対するワクチンとして理想的な系である。本研究は、乳酸菌を利用した安全かつ汎用性の高い粘膜ワクチン系の基盤技術の開発という学術的意義を持つ。本研究成果をさらに発展させ、多様な病原体に対する粘膜ワクチン開発に応用することで、様々な感染症対策に寄与できると考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (18 results)

All 2022 2021 2020 2019 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Intimate Adhesion Is Essential for the Pathogen-Specific Inflammatory and Immune Responses in the Gut of Mice Infected with <i>Citrobacter rodentium</i>2021

    • Author(s)
      Takahashi Keita、Sugiyama Tsuyoshi、Tokunoh Nagisa、Tsurumi Shun、Koshizuka Tetsuo、Inoue Naoki
    • Journal Title

      ImmunoHorizons

      Volume: 5 Issue: 10 Pages: 870-883

    • DOI

      10.4049/immunohorizons.2100087

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Eosinophils are the main cellular targets for oral gene delivery using Lactic acid bacteria.2020

    • Author(s)
      Keita Takahashi, Nozomi Orito, Daiki Yanagisawa, Ayumu Yano, Yusuke Mori, Naoki Inoue
    • Journal Title

      Vaccine

      Volume: 38 Issue: 17 Pages: 3330-3338

    • DOI

      10.1016/j.vaccine.2020.02.084

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Current Issues Regarding the Application of Recombinant Lactic Acid Bacteria to Mucosal Vaccine Carriers2019

    • Author(s)
      Keita Takahashi, Nozomi Orito, Nagisa Tokunoh, Naoki Inoue
    • Journal Title

      Applied microbiology and biotechnology

      Volume: 103 Issue: 15 Pages: 5947-5955

    • DOI

      10.1007/s00253-019-09912-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 細菌様粒子(BLP)アジュバントを用いた経鼻ワクチンの腸管感染症に対する防御効果に関する研究2022

    • Author(s)
      辻井彩人、須藤晴香、徳納渚沙、川嶋更奈、髙橋圭太、腰塚哲朗、井上直樹
    • Organizer
      第142回日本薬学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 乳酸菌を送達体とした経口DNAワクチン系に関する研究2022

    • Author(s)
      栁澤大貴、小林 靖、髙橋圭太、腰塚哲朗、井上直樹
    • Organizer
      第142回日本薬学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The effect of antigen binding and administration route of BLP on its immunogenicity2022

    • Author(s)
      Haruka Sudo, Ayato Tsujii, Tetsuo Koshizuka, Naoki Inoue, Keita Takahashi
    • Organizer
      第95回日本細菌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Intimate adhesion of Citrobacter rodentium is the cue to initiate anti-pathogen immune2022

    • Author(s)
      Keita Takahashi,† Tsuyoshi Sugiyama, Nagisa Tokunoh, Shun Tsurumi, Tetsuo Koshizuka, Naoki Inoue
    • Organizer
      第95回日本細菌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Evaluation of the mucosal vaccine system using bacterium-like particles prepared from L. lactis2020

    • Author(s)
      Nagisa Tokunoh, Keita Takahashi, Nozomi Orito, Daiki Yanagisawa, Naoki Inoue
    • Organizer
      第93回日本細菌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Eosinophils are the main cellular target for DNA delivery from orally administrated L. lactis2020

    • Author(s)
      Daiki Yanagisawa, Nozomi Orito, Keita Takahashi, Nagisa Tokunoh, Naoki Inoue
    • Organizer
      第93回日本細菌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Oral immunization with antigen/adjuvant co-producing Lactococcus lactis2020

    • Author(s)
      Keita Takahashi, Nagisa Tokunoh, Daiki Yanagisawa, Naoki Inoue
    • Organizer
      第93回日本細菌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Listeria adhesion protein increases the DNA delivery efficiency of Internalin A-expressing invasive Lactococcus lactis2019

    • Author(s)
      Nozomi Orito, Keita Takahashi, Naoki Inoue
    • Organizer
      第92回日本細菌学会
    • Related Report
      2019 Research-status 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92回日本細菌学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of the oral vaccine system using lactic acid bacteria2019

    • Author(s)
      Keita Takahashi, Naoki Inoue
    • Organizer
      第31回微生物シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] 細菌様粒子(BLP)を抗原送達体として用いる経口粘膜ワクチン系の構築と その免疫誘導能の検討2019

    • Author(s)
      徳納渚沙、髙橋圭太、折戸希、柳澤大貴、井上直樹
    • Organizer
      第23回日本ワクチン学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 細菌様粒子(BLP)を抗原送達体として用いる 経口粘膜ワクチン系の構築とその免疫誘導能の検討2019

    • Author(s)
      徳納渚沙、髙橋圭太、折戸希、柳澤大貴、井上直樹
    • Organizer
      第10回岐阜薬科大学機能性健康食品研究講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of cellular targets for DNA delivery from recombinant L. lactis strains in vivo2019

    • Author(s)
      Keita Takahashi, Nozomi Orito, Daiki Yanagisawa, Naoki Inoue
    • Organizer
      27th European Society of Gene and Cell Therapy
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 岐阜薬科大学 感染制御学研究室

    • URL

      https://www.gifu-pu.ac.jp/lab/kansen/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 岐阜薬科大学 生命薬学大講座 感染制御学研究室 ホームページ

    • URL

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

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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