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Identification of Epitopes Targeted by Neutralizing Antibodies Against SARS-CoV-2

Research Project

Project/Area Number 21K09078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionOsaka Metropolitan University (2022-2023)
Osaka City University (2021)

Principal Investigator

Kaku Natsuko  大阪公立大学, 大学院医学研究科, 講師 (10899355)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsSARS-CoV-2 / COVID-19 / エピトープ / RBD / 中和抗体 / 結合親和性 / ペプチドマッピング / mRNAワクチン / 新型コロナウイルス感染症(COVID-19) / 受容体結合ドメイン(RBD) / ペプチドマイクロアレイ / ペプチドアレイ
Outline of Research at the Start

SARS-CoV-2感染症の臨床症状は,無症状からCOVID-19重症肺炎,死亡に至るまで幅広く,重症化移行は急速で予測困難である.重症COVID-19患者血清はSARS-CoV-2抗体価が高くウイルス中和活性も高いとされるが,自然発生的抗体はポリクロ ーナルで患者毎に多様なため,これらポリクローナル抗体のエピトープの多様性が個人におけるウイルス感染防御の有効性を決定していると考えられる.本研究では,1,000以上の検体において,独自のペプチドアレイにより検出した患者血清ポリクローナル抗体の多様なエピトープから,高い中和活性を持つ抗体が標的とするエピトープを高解像度に同定する.

Outline of Final Research Achievements

We elucidated the epitope profiles of COVID-19 mRNA vaccine recipients and naturally infected individuals using an RBD peptide immobilized microarray of SARS-CoV-2. The findings revealed that vaccine-induced antibodies are more broadly distributed across the RBD compared to those from natural infection. The relatively lower neutralizing antibody titers observed in vaccine sera, as compared to natural infection sera, may be due to less efficient epitope maturation in the humoral response induced by the vaccine. Assays using a mutation panel demonstrated that the epitope diversity in vaccine sera potentially reduces the ability of the rapidly evolving virus to evade neutralizing antibodies, thereby providing an advantage to vaccine-induced immunity.

Academic Significance and Societal Importance of the Research Achievements

本研究により中和抗体の標的となるエピトープが同定され、個別のエピトーププロファイルから、患者血清に含まれる抗体の中和活性を病原性ウイルスを用いずに予測可能となった。抗体の結合親和性は自然感染後/ワクチン接種後、時間とともに上昇し、ウイルス中和活性と相関する一方で、汎用臨床検査装置によっては抗体価が結合親和性とそれほど強く相関しないものがあるといった懸念を示した。さらに、ワクチン接種後のエピトープ成熟過程において、年齢によって大きな差異があること、自然感染後のワクチン接種はワクチン接種のみと比較してより高いウイルス中和抗体を獲得できることを明らかとし、今後のワクチン接種施策に資する知見を得た。

Report

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

    (21 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 11 results) Presentation (8 results) (of which Int'l Joint Research: 2 results)

  • [Int'l Joint Research] CICES/National Rosales Hospital, San Salvador/El Salvador National Institute of Health(エルサルバドル)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] INRB(コンゴ民主共和国)

    • 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] 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] 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] Detecting Waning Serological Response with Commercial Immunoassays: 18-Month Longitudinal Follow-up of Anti-SARS-CoV-2 Nucleocapsid Antibodies2022

    • Author(s)
      Nakagama Yu、Komase Yuko、Kaku Natsuko、Nitahara Yuko、Tshibangu-Kabamba Evariste、Tominaga Tomoyo、Tanaka Hiroko、Yokoya Tomoaki、Hosokawa Minako、Kido Yasutoshi
    • Journal Title

      Microbiology Spectrum

      Volume: 10 Issue: 4

    • DOI

      10.1128/spectrum.00986-22

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [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
  • [Journal Article] Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6?months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan2022

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

      Vaccine

      Volume: 40 Issue: 38 Pages: 5631-5640

    • DOI

      10.1016/j.vaccine.2022.08.018

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [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] Antibody testing as the guide to our living with COVID-192022

    • Author(s)
      KAKU Natsuko、NAKAGAMA Yu、NITAHARA Yuko、KIDO Yasutoshi
    • Journal Title

      Japanese Journal of Thrombosis and Hemostasis

      Volume: 33 Issue: 3 Pages: 338-346

    • DOI

      10.2491/jjsth.33.338

    • ISSN
      0915-7441, 1880-8808
    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] A Dual-Antigen SARS-CoV-2 Serological Assay Reflects Antibody Avidity2022

    • Author(s)
      Nakagama Yu、Nitahara Yuko、Kaku Natsuko、Tshibangu-Kabamba Evariste、Kido Yasutoshi
    • Journal Title

      Journal of Clinical Microbiology

      Volume: 60 Issue: 2

    • DOI

      10.1128/jcm.02262-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Longitudinal ventilatory ratio monitoring for COVID-19: its potential in predicting severity and assessing treatment response2021

    • Author(s)
      Kaku Natsuko、Nakagama Yu、Shirano Michinori、Shinomiya Sari、Shimazu Kazuhiro、Yamazaki Katsuaki、Maehata Yoshito、Morita Ryo、Nitahara Yuko、Yamamoto Hiromasa、Mizobata Yasumitsu、Kido Yasutoshi
    • Journal Title

      Critical Care

      Volume: 25 Issue: 1 Pages: 366-366

    • DOI

      10.1186/s13054-021-03768-2

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients2021

    • Author(s)
      Nitahara Yuko、Nakagama Yu、Kaku Natsuko、Candray Katherine、Michimuko Yu、Tshibangu-Kabamba Evariste、Kaneko Akira、Yamamoto Hiromasa、Mizobata Yasumitsu、Kakeya Hiroshi、Yasugi Mayo、Kido Yasutoshi
    • Journal Title

      Microbiology Spectrum

      Volume: 9 Issue: 3

    • DOI

      10.1128/spectrum.00965-21

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SARS-CoV-2 mRNAワクチン接種後の接種間隔を長くすると、3回目および4回目 接種後抗体価は上昇する2023

    • Author(s)
      松浦知香、福島若葉、加瀬哲男、大藤さとこ、近藤亨子、吹田安佐詠、迎恵美子、 小西絢子、笠松彩音、城戸康年、中釜悠、加来奈津子、掛屋弘、金子幸弘、廣田 良夫
    • Organizer
      第27回ワクチン学会
    • Related Report
      2023 Annual Research Report
  • [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
      日本小児科学会
    • Related Report
      2022 Research-status Report
  • [Presentation] COVID-19のワクチン接種後抗体に及ぼす年齢の影響2022

    • Author(s)
      中釜 幸恵, 中釜 悠, 駒瀬 裕子, 工藤 正治, 今井 匠, 仁田原 裕子, 加来 奈津子, チバング・エバリステ , 城戸 康年
    • Organizer
      日本渡航医学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Covid-19パンデミックが医療システムへ及ぼした影響 日本、エルサルバドル、コンゴ民主共和国の医療従事者におけるSARS-CoV-2血清有病率の比較調査2022

    • Author(s)
      中釜 悠, チバング・エバリステ , カンドライ・カテリン , 加来 奈津子, 中釜 幸恵, 仁田原 裕子, 金子 明, マリア・ロドリゲス , リーナ・ドミンゲス , 城戸 康年
    • Organizer
      日本渡航医学会
    • 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)
      中釡 悠, カンドライ・カテリン , 加来 奈津子, チバング・エバリステ , 仁田原 裕子, 城戸 康年
    • Organizer
      日本生化学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Avidity maturation favors convalescents over vaccinated individuals granting breadth in neutralizability and tolerance against SARS-CoV-2 variants2022

    • Author(s)
      Natsuko Kaku, Yu Nakagama, Yuko Nitahara, Hiroshi Kakeya, Yasutoshi Kido
    • Organizer
      ASM Microbe
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Avidity Maturation Favors Convalescents Over Vaccinated Individuals Granting Breadth in Neutralizability and Tolerance Against SARS-CoV-2 Variants2022

    • Author(s)
      Natsuko Kaku, Yu Nakagama, Yuko Nitahara, Yasutoshi Kido
    • Organizer
      ASM microbe
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] COVID-19 mRNAワクチン接種者におけるSARS-CoV-2スパイクタンパク質受容体結合ドメインの高解像度線形エピトープマッピング解析2021

    • Author(s)
      仁田原 裕子 , 中釜 悠 , 加来 奈津子 , Tshibangu-Kabamba Evariste , 金子 明 , 安木 真世 , 城戸 康年
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report

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

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