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Cross-protective antibody response in the lungs upon influenza virus infection

Research Project

Project/Area Number 19K17656
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
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, 免疫部, 主任研究官 (40749016)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords交差防御抗体 / インフルエンザウイルス / ワクチン / ユニバーサルワクチン / B細胞 / インフルエンザ / インフルエンザワクチン / 免疫学
Outline of Research at the Start

インフルエンザウイルスは抗原変異を繰り返すため、現行のインフルエンザワクチンでは終生免疫を付与することはできない。本研究は、抗原変異インフルエンザウイルスにも有効なユニバーサルワクチン開発に向け、ウイルス感染時の肺組織で誘導される交差防御抗体応答の詳細なメカニズム解明を目的としている。

Outline of Final Research Achievements

In this study, we focus on the antigenic structure which can induce cross-protective antibody response to obtain the informations for the development of universal influenza vaccine seeds. Here, we found that unique, distinct antibody repertoires which bind better to hemagglutinin antigens with membrane fusion-form than to that with native-form were selected in the lungs but not in secondly lymphoid organs, such as spleen. This data suggests that hemagglutinin structure exposing conserved epitopes such as LAH epitope is arisen and then induces cross-protective antibody response in the lungs after viral infection. Furthermore, we optimized the experimental conditions for identification of the antigenic structure on antigen-presenting cells.

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所謂ユニバーサルインフルエンザワクチンの社会的要請は高く、新規ワクチン剤形シーズ開発が精力的に進められているが実用化は未だ達成されていない。本研究では、世界で主に進められている分子構造学的アプローチとは異なり、ウイルス感染後の交差防御抗体応答を解析するという免疫学的アプローチを基軸とすることでワクチンデザイン戦略における新たな科学的知見が取得した。今後ユニバーサルワクチンシーズ開発と実用化に向けたさらなる進捗が期待できると考えられる。

Report

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

    (9 results)

All 2020 2019

All Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 4 results)

  • [Journal Article] Memory B Cells in Local and Systemic Sites2020

    • Author(s)
      Moriyama Saya、Adachi Yu、Tonouchi Keisuke、Takahashi Yoshimasa
    • Journal Title

      Adv Exp Med Biol

      Volume: 1254 Pages: 55-62

    • DOI

      10.1007/978-981-15-3532-1_5

    • ISBN
      9789811535314, 9789811535321
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hide and seek: interplay between influenza viruses and B cells2020

    • Author(s)
      Kuraoka Masayuki、Adachi Yu、Takahashi Yoshimasa
    • Journal Title

      International Immunology

      Volume: 32 Issue: 9 Pages: 605-611

    • DOI

      10.1093/intimm/dxaa028

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stereotyped B-cell response that counteracts antigenic variation of influenza viruses2020

    • Author(s)
      Tonouchi Keisuke、Adachi Yu、Moriyama Saya、Sano Kaori、Tabata Koshiro、Ide Keigo、Takeyama Haruko、Suzuki Tadaki、Takahashi Yoshimasa
    • Journal Title

      International Immunology

      Volume: 32 Issue: 9 Pages: 613-621

    • DOI

      10.1093/intimm/dxaa038

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bim establishes the B-cell repertoire from early to late in the immune response2020

    • Author(s)
      Sugimoto-Ishige Akiko、Harada Michishige、Tanaka Miho、Terooatea Tommy、Adachi Yu、Takahashi Yoshimasa、Tanaka Takashi、Burrows Peter D、Hikida Masaki、Takemori Toshitada
    • Journal Title

      International Immunology

      Volume: 33 Issue: 2 Pages: 79-90

    • DOI

      10.1093/intimm/dxaa060

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism2019

    • Author(s)
      Watanabe A, McCarthy KR, Kuraoka M, Schmidt AG, Adachi Y, Onodera T, Tonouchi K, Caradonna TM, Bajic G, Song S, McGee CE, Sempowski GD, Feng F, Urick P, Kepler TB, Takahashi Y, Harrison SC, Kelsoe G.Influenza
    • Journal Title

      Cell

      Volume: 177(5) Issue: 5 Pages: 1124-1135

    • DOI

      10.1016/j.cell.2019.03.048

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Requirement for memory B-cell activation in protection from heterologous influenza virus reinfection2019

    • Author(s)
      Leach Sarah、Shinnakasu Ryo、Adachi Yu、Momota Masatoshi、Makino-Okamura Chieko、Yamamoto Takuya、Ishii Ken J、Fukuyama Hidehiro、Takahashi Yoshimasa、Kurosaki Tomohiro
    • Journal Title

      International Immunology

      Volume: 31 Issue: 12 Pages: 771-779

    • DOI

      10.1093/intimm/dxz049

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope2019

    • Author(s)
      Bajic G, Maron MJ, Adachi Y, Onodera T, McCarthy KR, McGee CE, Sempowski GD, Takahashi Y, Kelsoe G, Kuraoka M, Schmidt AG.Influenza
    • Journal Title

      Cell Host and Microbe

      Volume: 25(6) Issue: 6 Pages: 827-835

    • DOI

      10.1016/j.chom.2019.04.003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exposure of an occluded hemagglutinin epitope drives selection of a class of cross-protective influenza antibodies2019

    • Author(s)
      Adachi Yu、Tonouchi Keisuke、Nithichanon Arnone、Kuraoka Masayuki、Watanabe Akiko、Shinnakasu Ryo、Asanuma Hideki、Ainai Akira、Ohmi Yusuke、Yamamoto Takuya、Ishii Ken J.、Hasegawa Hideki、Takeyama Haruko、Lertmemongkolchai Ganjana、Kurosaki Tomohiro、Ato Manabu、Kelsoe Garnett、Takahashi Yoshimasa
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41467-019-11821-6

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【インフルエンザウイルスと防御】隠れたインフルエンザヘマグルチニンエピトープに対する交差防御抗体2019

    • Author(s)
      安達 悠, 登内 奎介, 高橋 宜聖
    • Journal Title

      ウイルス

      Volume: 69 Pages: 161-168

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2022-01-27  

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