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Analysis of a tetrameric secretory IgA antibody production

Research Project

Project/Area Number 17K08386
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Suzuki Tadaki  国立感染症研究所, 感染病理部, 部長 (30527180)

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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsIgA抗体 / 抗ウイルス活性 / 四量体分泌型IgA抗体 / インフルエンザ / 分泌型IgA抗体 / 抗体医薬 / 蛋白質 / IgA
Outline of Final Research Achievements

The mechanism of antiviral activity enhancement by tetramerization of secretory IgA antibody, which is important for the prevention of respiratory virus infections such as influenza, had been unknown. In this study, we developed a monoclonal tetrameric secretory IgA antibody production technique and succeeded in producing various forms of IgA antibody having the identical variable region. This technique revealed that the tetramerization of IgA antibody improved target breadth, but not peak potency of antiviral activities. The results of this research are expected to lead to the development of novel monoclonal antibody therapeutics using the monoclonal tetrameric secretory IgA antibody production technology.

Academic Significance and Societal Importance of the Research Achievements

今回の研究で我々が開発したモノクローナル四量体SIgA抗体作製技術は、抗ウイルス抗体の作用機構を解明する基礎研究のツールとしてだけでなく、粘膜組織に特化した新たな抗体医薬のプラットフォームとしての応用も可能と考えられる。現在、様々な分野で抗体医薬が重要視されているが、現在までに実用化されている抗体医薬は全てIgG型抗体医薬のみである。IgGとは異なる性質を有しているIgAを基本骨格とするIgA型抗体医薬の開発は抗体医薬の可能性をさらに大きく広げることが期待でき、本成果は基礎ウイルス研究に限らず今後の医薬品開発にとって重要な成果と考えられる。

Report

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

    (22 results)

All 2020 2019 2018 2017

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 3 results) Presentation (12 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Human immune responses elicited by an intranasal inactivated H5 influenza vaccine2020

    • Author(s)
      Ainai Akira、Riet Elly、Ito Ryo、Ikeda Kazuyuki、Senchi Kyosuke、Suzuki Tadaki、Tamura Shin‐ichi、Asanuma Hideki、Odagiri Takato、Tashiro Masato、Kurata Takeshi、Multihartina Pretty、Setiawaty Vivi、Pangesti Krisna Nur Andriana、Hasegawa Hideki
    • Journal Title

      Microbiology and Immunology

      Volume: 64 Issue: 4 Pages: 313-325

    • DOI

      10.1111/1348-0421.12775

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IgA抗体によるインフルエンザウイルス感染防御2019

    • Author(s)
      鈴木忠樹、長谷川秀樹
    • Journal Title

      ウイルス

      Volume: 69 Pages: 153-160

    • Related Report
      2019 Annual Research Report
  • [Journal Article] IgA tetramerization improves target breadth but not peak potency of functionality of anti-influenza virus broadly neutralizing antibody2019

    • Author(s)
      Saito Shinji、Sano Kaori、Suzuki Tadaki、Ainai Akira、Taga Yuki、Ueno Tomonori、Tabata Koshiro、Saito Kumpei、Wada Yuji、Ohara Yuki、Takeyama Haruko、Odagiri Takato、Kageyama Tsutomu、Ogawa-Goto Kiyoko、Multihartina Pretty、Setiawaty Vivi、Pangesti Krisna Nur Andriana、Hasegawa Hideki
    • Journal Title

      PLOS Pathogens

      Volume: 15 Issue: 1 Pages: e1007427-e1007427

    • DOI

      10.1371/journal.ppat.1007427

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IgA polymerization contributes to efficient virus neutralization on human upper respiratory mucosa after intranasal inactivated influenza vaccine administration2018

    • Author(s)
      Terauchi Yoshihiko、Sano Kaori、Ainai Akira、Saito Shinji、Taga Yuki、Ogawa-Goto Kiyoko、Tamura Shin-ichi、Odagiri Takato、Tashiro Masato、Fujieda Mikiya、Suzuki Tadaki、Hasegawa Hideki
    • Journal Title

      Human Vaccines & Immunotherapeutics

      Volume: - Issue: 6 Pages: 1351-1361

    • DOI

      10.1080/21645515.2018.1438791

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intranasal inactivated influenza vaccines for the prevention of seasonal influenza epidemics2018

    • Author(s)
      Sano Kaori、Ainai Akira、Suzuki Tadaki、Hasegawa Hideki
    • Journal Title

      Expert Review of Vaccines

      Volume: 17 Issue: 8 Pages: 687-696

    • DOI

      10.1080/14760584.2018.1507743

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate2017

    • Author(s)
      Ainai Akira、Suzuki Tadaki、Tamura Shin-ichi、Hasegawa Hideki
    • Journal Title

      Viral Immunology

      Volume: 30 Issue: 6 Pages: 451-462

    • DOI

      10.1089/vim.2017.0022

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functional and structural characteristics of secretory IgA antibodies elicited by mucosal vaccines against influenza virus2017

    • Author(s)
      Suzuki Tadaki、Ainai Akira、Hasegawa Hideki
    • Journal Title

      Vaccine

      Volume: 35 Issue: 39 Pages: 5297-5302

    • DOI

      10.1016/j.vaccine.2017.07.093

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The road to a more effective influenza vaccine: Up to date studies and future prospects2017

    • Author(s)
      Sano Kaori、Ainai Akira、Suzuki Tadaki、Hasegawa Hideki
    • Journal Title

      Vaccine

      Volume: 35 Issue: 40 Pages: 5388-5395

    • DOI

      10.1016/j.vaccine.2017.08.034

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] cGAMP Promotes Germinal Center Formation and Production of IgA in Nasal-Associated Lymphoid Tissue2017

    • Author(s)
      Takaki Hiromi、Takashima Ken、Oshiumi Hiroyuki、Ainai Akira、Suzuki Tadaki、Hasegawa Hideki、Matsumoto Misako、Seya Tsukasa
    • Journal Title

      Medical Sciences

      Volume: 5 Issue: 4 Pages: 35-35

    • DOI

      10.3390/medsci5040035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production2017

    • Author(s)
      Takaki H、Kure S、Oshiumi H、Sakoda Y、Suzuki T、Ainai A、Hasegawa H、Matsumoto M、Seya T
    • Journal Title

      Mucosal Immunology

      Volume: 11 Issue: 1 Pages: 82-96

    • DOI

      10.1038/mi.2017.48

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 経鼻接種型不活化ワクチンと皮下接種型不活化ワクチンにより誘導された 抗インフルエンザ抗体の質についての比較解析2019

    • Author(s)
      佐野 芳、黒澤 信幸、齊藤 慎二、相内 章、鈴木 忠樹、磯部 正治、 長谷川 秀樹
    • Organizer
      第23回日本ワクチン学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A型インフルエンザウイルスに対する交差感染防御免疫への非中和IgA抗体の役割2019

    • Author(s)
      奥谷 公亮、吉田 玲子、マンズール ラシッド、齊藤 慎二、鈴木 忠樹、市居 修、東 秀明、高田 礼人
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 経鼻インフルエンザワクチンで誘導された抗HA stalk抗体のHAおよびNAの立体障害による抗ウイルス効果の発現2019

    • Author(s)
      佐野 芳、齊藤 慎二、鈴木 忠樹、小谷 治、van Riet Elly、相内 章、田畑 耕史郎、高橋 宜聖、横山 勝、佐藤 裕徳、長谷川 秀樹
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] In vitroにおける四量体分泌型IgA抗体形成機構の解明2019

    • Author(s)
      田畑耕史郎、鈴木忠樹、佐野芳、齊藤慎二、相内章、大場靖子、長谷川秀樹、澤洋文
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Enhancement and Extension in Anti-viral Functions of Influenza Virus Broadly Neutralizing Antibodies by IgA Multimerization2019

    • Author(s)
      Kaori Sano, Shinji Saito, Akira Ainai, Koshiro Tabata, Tadaki Suzuki, and Hideki Hasegawa
    • Organizer
      Keystone Symposia ~Molecular Approaches to Vaccines and Immune Monitoring~
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Improvement in Functionality of Anti-Influenza Virus Antibodies Conferred by IgA Tetramerization2019

    • Author(s)
      Kaori Sano, Tadaki Suzuki, Shinji Saito, Akira Ainai, Koshiro Tabata, and Hideki Hasegawa
    • Organizer
      Influenza and Other Infections
    • Related Report
      2018 Research-status Report
  • [Presentation] 経鼻ワクチンにより誘導された抗インフルエンザHAステム抗体のウイルス感染防御機構2018

    • Author(s)
      佐野芳, 齊藤慎二, 小谷治, 相内章, Elly van Riet, 田畑耕史郎, 高橋宜聖, 横山勝, 佐藤裕徳, 鈴木忠樹, 長谷川秀樹
    • Organizer
      第22回日本ワクチン学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Extending an Anti-Viral Function of an Intranasal Vaccine-Derived Anti-Influenza Virus Hemagglutinin Stalk Antibody by IgA Polymerization2018

    • Author(s)
      Sano K, Saito S, Suzuki T, Kotani O, van Riet E, Ainai A, Tabata K, Takahashi Y, Yokoyama M, Sato H, Ogawa-Goto K, Hasegawa H
    • Organizer
      The 10th Global Virus Network Meeting: Eradication and Control of (Re-)Emerging Viruses
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Secretory componentによる分泌型四量体IgA抗体形成促進の分子機構解析2018

    • Author(s)
      田畑耕史郎、鈴木忠樹、佐野芳、齊藤慎二、藤井信、齋藤訓平、原田陽介、相内章、長谷川秀樹
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 経鼻インフルエンザワクチンで誘導された広域中和抗体の多量体化による活性増強2017

    • Author(s)
      佐野芳、齊藤慎二、鈴木忠樹、相内章、小谷治、Elly van Riet、田畑耕史郎、藤井信、高橋宜聖、後藤希代子、影山努、長谷川秀樹
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 経鼻不活化インフルエンザワクチン接種により誘導される粘膜抗体の性状解析2017

    • Author(s)
      鈴木忠樹、寺内芳彦、相内章、齊藤慎二、多賀祐喜、大原有樹、山口喜之、小田切孝人、田代眞人、後藤希代子、長谷川秀樹
    • Organizer
      第21回日本ワクチン学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] モノクローナル多量体IgA抗体作製法を用いた分泌型IgA抗体の抗ウイルス活性の解析2017

    • Author(s)
      佐野芳、齊藤慎二、鈴木忠樹、上野智規、多賀祐喜、Elly van Riet、相内章、田畑耕史郎、藤井信、高橋宜聖、後藤希代子、長谷川秀樹
    • Organizer
      第21回日本ワクチン学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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