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Characterizing human cross-protective antibodies for a universal influenza vaccine

Research Project

Project/Area Number 21K08192
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionNational Institute of Infectious Diseases

Principal Investigator

Adachi Yu  国立感染症研究所, 治療薬・ワクチン開発研究センター, 主任研究官 (40749016)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords交差防御抗体 / インフルエンザウイルス / ヒト交差防御抗体 / インフルエンザ / 免疫 / ワクチン / 抗体
Outline of Research at the Start

申請者は、インフルエンザ感染マウスモデルにおける交差防御抗体の発達に関する研究を進めてきており、蓄積した免疫学的データから着想を得て、新規ユニバーサルワクチン抗原の開発に成功して知財化を完了した。
そこで本研究では、新たなワクチンデザイン戦略における科学的基盤の整備に向け、新規ワクチンにより誘導される“極めて優れた交差性を発揮するヒト抗体レパトア”に焦点を当て、その性状を解明することを目的としている。

Outline of Final Research Achievements

In this study, we aimed to clarify the properties of human cross-protective antibodies for developing a universal vaccine that is effective against antigenically mutated influenza viruses. As a result, we found that the human cross-protective antibody, named LAH31, recognizes to an epitope formed only in the membrane fusion structure of the hemagglutinin antigen. Furthermore, we found that mutation insertion in the antibody light chain gene of LAH31 is important for acquiring broad cross-reactivity.

Academic Significance and Societal Importance of the Research Achievements

抗原変異インフルエンザウイルスにも有効な交差防御抗体の誘導を目的としたユニバーサルインフルエンザワクチンの社会的妖精は高い一方、いまだその実用化は達成されていない。本研究では、臨床応用が進められている新規ワクチンの主な誘導ターゲットであるヒト交差防御抗体の結合様式および交差結合性の獲得機序を明らかとしたことで、今後の新規ワクチンのヒト応用および実用化へと繋がると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (3 results)

All 2023 2022 2021

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

  • [Journal Article] Structural basis for cross-group recognition of an influenza virus hemagglutinin antibody that targets postfusion stabilized epitope2023

    • Author(s)
      Tonouchi K, Adachi Y, Suzuki T, Kuroda D, Nishiyama A, Yumoto K, Takeyama H, Suzuki T, Hashiguchi T, Takahashi Y.
    • Journal Title

      PLoS Pathog .

      Volume: 19(8) Issue: 8 Pages: e1011554-e1011554

    • DOI

      10.1371/journal.ppat.1011554

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Saliva as a useful tool for evaluating upper mucosal antibody response to influenza2022

    • Author(s)
      Tsunetsugu-Yokota Yasuko、Ito Sayaka、Adachi Yu、Onodera Taishi、Kageyama Tsutomu、Takahashi Yoshimasa
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 2 Pages: e0263419-e0263419

    • DOI

      10.1371/journal.pone.0263419

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influenza virus infection expands the breadth of antibody responses through IL-4 signalling in B cells2021

    • Author(s)
      Miyauchi Kosuke、Adachi Yu、Tonouchi Keisuke、Yajima Taiki、Harada Yasuyo、Fukuyama Hidehiro、Deno Senka、Iwakura Yoichiro、Yoshimura Akihiko、Hasegawa Hideki、Yugi Katsuyuki、Fujii Shin-ichiro、Ohara Osamu、Takahashi Yoshimasa、Kubo Masato
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41467-021-24090-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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