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Antibody avidity maturation as index for Immune resilience against SARS-CoV-2

Research Project

Project/Area Number 22K15927
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOsaka Metropolitan University

Principal Investigator

Nakagama Yu  大阪公立大学, 大学院医学研究科, 准教授 (60846880)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsSARS-CoV-2 / 中和抗体 / 親和性成熟 / ワクチン / 自然感染 / COVID-19 / エピトープ / アビディティ / 抗体力価 / 抗体成熟 / 変異株 / アビディティー
Outline of Research at the Start

次々に出現する新型コロナウイルス変異株の脅威に、我々は追加ワクチン接種による免疫増強や、小児人口のワクチンカバレッジ強化、の意思決定を迫られている。しかし、その是非を議論するための科学的根拠は脆弱であり、ワクチン誘導免疫の特性について理解の途上にある。本提案では、回復者及びワクチン接種者血清中にみられる「抗体親和性成熟化」が「ウイルス中和活性」の規定因子であることを立証し、構造生物学的プロセスを生物学的アウトカムへと繋げる。抗原抗体反応の親和性を表す「アビディティー」のモニタリングから、抗体成熟化過程の分子基盤を解明し、ポストワクチン時代における「防御免疫指標」の1つに提案することを目指す。

Outline of Final Research Achievements

Antibody maturation is important for viral neutralization, especially for broad neutralizing capacity, supporting the relevance of additional booster vaccination due to concerns about delayed avidity maturation in the vaccinees. In vitro evidence, showing strong association between SARS-CoV-2 high affinity antibodies and broad cross-neutralizability, clearly explains from the molecular perspective the lower number of real-world re-infections compared with the higher number of post-vaccination breakthrough infections. The findings altogether support adaptive decision making regarding vaccination strategies. The project further assessed the advantages of hybrid immunity, as well as the adaptive immunity development in vulnerable populations including cancer patients, octogenarians, and immunocompromised patients, from the view point of antibody avidity maturation kinetics.

Academic Significance and Societal Importance of the Research Achievements

抗体アビディティ成熟は、SARS-CoV-2中和能、特に中和能広域化に重要であることが示された。ワクチン接種においてはアビディティ成熟の遅延が懸念されるため、追加ブースター接種の妥当性が支持された。SARS-CoV-2感染回復者が持つ高親和性抗体が、変異株に対しても広域な交差中和活性を発揮しうる、というin vitroのエビデンスは、リアルワールドにおいて回復者が再感染を起こす頻度が低いこと、ワクチン被接種者ブレイクスルー感染の頻度が多いことを、その分子背景から巧妙に説明した。本研究成果によって、ワクチン接種戦略に関するアクティブかつアダプティブな意思決定を支援するエビデンスが創出された。

Report

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

    (20 results)

All 2024 2023 2022 Other

All Int'l Joint Research (6 results) Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] サウスカロライナ大学/ワシントン大学(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 国立衛生研究所(エルサルバドル)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] 国立医生物学研究所(コンゴ民主共和国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Hospital National Rosales/National Institute of Health(エルサルバドル)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] 国立医生物学研究所(コンゴ民主共和国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] サウスカロライナ大学(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Factors impacting antibody kinetics, including fever and vaccination intervals, in SARS-CoV-2-na?ve adults receiving the first four mRNA COVID-19 vaccine doses2024

    • Author(s)
      Matsuura Tomoka、Fukushima Wakaba、Nakagama Yu、Kido Yasutoshi、Kase Tetsuo、Kondo Kyoko、Kaku Natsuko、Matsumoto Kazuhiro、Suita Asae、Mukai Emiko、Nitahara Yuko、Konishi Ayako、Kasamatsu Ayane、Nakagama Sachie、Nakagami-Yamaguchi Etsuko、Ohfuji Satoko、Kaneko Yukihiro、Kaneko Akira、Kakeya Hiroshi、Hirota Yoshio
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 7217-7217

    • DOI

      10.1038/s41598-024-57931-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neutralization sensitivity of SARS-CoV-2 Omicron variants FL.1 and GE.1 by therapeutic antibodies and XBB sera2024

    • Author(s)
      Lee Joseph、Naoe Youichi、Bang Uikyu、Nakagama Yu、Saito Akatsuki、Kido Yasutoshi、Hotta Akitsu
    • Journal Title

      Virology

      Volume: 595 Pages: 110067-110067

    • DOI

      10.1016/j.virol.2024.110067

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Characteristics of epitope dominance pattern and cross-variant neutralisation in 16 SARS-CoV-2 mRNA vaccine sera2023

    • Author(s)
      Yasugi Mayo、Nakagama Yu、Kaku Natsuko、Nitahara Yuko、Hatanaka Noritoshi、Yamasaki Shinji、Kido Yasutoshi
    • Journal Title

      Vaccine

      Volume: 41 Issue: 42 Pages: 6248-6254

    • DOI

      10.1016/j.vaccine.2023.08.076

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amino acid catabolite markers for early prognostication of pneumonia in patients with COVID-192023

    • Author(s)
      Maeda Rae、Seki Natsumi、Uwamino Yoshifumi、Wakui Masatoshi、Nakagama Yu、Kido Yasutoshi、Sasai Miwa、Taira Shu、Toriu Naoya、Yamamoto Masahiro、Matsuura Yoshiharu、Uchiyama Jun、Yamaguchi Genki、Hirakawa Makoto、Kim Yun-Gi、Mishima Masayo、Yanagita Motoko、Suematsu Makoto、Sugiura Yuki
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 8469-8469

    • DOI

      10.1038/s41467-023-44266-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response2023

    • Author(s)
      Nakagama Sachie、Nakagama Yu、Komase Yuko、Kudo Masaharu、Imai Takumi、Tshibangu-Kabamba Evariste、Nitahara Yuko、Kaku Natsuko、Kido Yasutoshi
    • Journal Title

      Frontiers in Immunology

      Volume: 14 Pages: 1-7

    • DOI

      10.3389/fimmu.2023.1087473

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination2023

    • Author(s)
      Nakagama Yu、Chi Sung-Gi、Minami Yosuke、Watanabe Reiko、Yamagishi Michiteru、Atsuko Uno、Kido Yasutoshi
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 29 Issue: 1 Pages: 112-114

    • DOI

      10.1016/j.jiac.2022.09.018

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity2022

    • Author(s)
      Nakagama Y、Candray K、Kaku N、Komase Y、Rodriguez-Funes M-V、Dominguez R、Tsuchida T、Kunishima H、Nagai E、Adachi E、Mumba N D 、Yamasue M、Komiya K、Hiramatsu K、Uemura N、Sugiura Y、Yasugi M、Yamagishi Y、Mikamo H、Shiraishi S、Izumo T、Nakagama S、Watanabe C、Nitahara Y、Tshibangu-Kabamba E、Kakeya H、Kido Y
    • Journal Title

      The Journal of Infectious Diseases

      Volume: 227 Issue: 6 Pages: 780-787

    • DOI

      10.1093/infdis/jiac492

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study2022

    • Author(s)
      Nakashima Kei、Ishida Masayuki、Matsui Hiroki、Yoshida Chihiro、Nagai Tatsuya、Shiraga Minoru、Nakaoka Hiroshi、Otsuka Yoshihito、Nakagama Yu、Kaku Natsuko、Nitahara Yuko、Kido Yasutoshi、Hirota Yoshio
    • Journal Title

      Human Vaccines & Immunotherapeutics

      Volume: 18 Issue: 6 Pages: 1-13

    • DOI

      10.1080/21645515.2022.2140549

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 新興・再興感染症の危機に即応し、医療適正化に資する血清疫学研究2023

    • Author(s)
      中釜悠
    • Organizer
      第31回日本医学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] SARS-CoV-2に対する血清抗体成熟化の臨床的意義2023

    • Author(s)
      中釜 悠,Candray Katherine,中釜 幸恵,加来 奈津子,仁田原 裕子,Tshibangu Evariste,城戸 康年
    • Organizer
      第126回 日本小児科学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 新興・再興感染症の危機に即応し、医療適正化に資する血清疫学研究2023

    • Author(s)
      中釜 悠
    • Organizer
      第31回 日本医学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] The impact of the Covid-19 pandemic on healthcare systems; multi-country com parison of SARS-CoV-2 seroprevalence among healthcare workers in Japan, El S alvador, and the Democratic Republic Of Congo2022

    • Author(s)
      Yu Nakagama, Katherine Candray, Natsuko Kaku, Evariste Tshibangu-Kabamba, Sachie Nakagama, Yuko Nitahara, Yasutoshi Kido
    • Organizer
      第63回 日本熱帯医学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 抗体アビディティー成熟の観点からみた、SARS-CoV-2ワクチン誘導免疫と自然感染に よる免疫の差異2022

    • Author(s)
      Yu Nakagama, Katherine Candray, Natsuko Kaku, Yuko Nitahara, Evariste Tshibangu-Kabamba, Yasutoshi Kido
    • Organizer
      第95回 日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] ANTIBODY AVIDITY MATURATION FAVORS SARS-COV-2 CONVALESCENTS OVER VACCINATED INDIVIDUALS GRANTING BREADTH IN NEUTRALIZABILITY AND TOLERANCE AGAINST VARIANTS2022

    • Author(s)
      Yu Nakagama, Katherine Candray, Natsuko Kaku, Sachie Nakagama, Chihiro Watanabe, Yuko Nitahara, Evariste Tshibangu-Kabamba, Yasutoshi Kido
    • Organizer
      JOINT INTERNATIONAL TROPICAL MEDICINE MEETING 2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2025-01-30  

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