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A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies

Author

Listed:
  • Chunyan Wang

    (Utrecht University)

  • Rien Haperen

    (Erasmus Medical Center
    Harbour BioMed)

  • Javier Gutiérrez-Álvarez

    (National Center for Biotechnology-Spanish National Research Council (CNB-CSIC))

  • Wentao Li

    (Utrecht University)

  • Nisreen M. A. Okba

    (Erasmus Medical Center)

  • Irina Albulescu

    (Utrecht University)

  • Ivy Widjaja

    (Utrecht University
    Merus N.V.)

  • Brenda Dieren

    (Utrecht University)

  • Raul Fernandez-Delgado

    (National Center for Biotechnology-Spanish National Research Council (CNB-CSIC))

  • Isabel Sola

    (National Center for Biotechnology-Spanish National Research Council (CNB-CSIC))

  • Daniel L. Hurdiss

    (Utrecht University)

  • Olalekan Daramola

    (Cell Culture and Fermentation Sciences, Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca)

  • Frank Grosveld

    (Erasmus Medical Center
    Harbour BioMed)

  • Frank J. M. Kuppeveld

    (Utrecht University)

  • Bart L. Haagmans

    (Erasmus Medical Center)

  • Luis Enjuanes

    (National Center for Biotechnology-Spanish National Research Council (CNB-CSIC))

  • Dubravka Drabek

    (Erasmus Medical Center
    Harbour BioMed)

  • Berend-Jan Bosch

    (Utrecht University)

Abstract

The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.

Suggested Citation

  • Chunyan Wang & Rien Haperen & Javier Gutiérrez-Álvarez & Wentao Li & Nisreen M. A. Okba & Irina Albulescu & Ivy Widjaja & Brenda Dieren & Raul Fernandez-Delgado & Isabel Sola & Daniel L. Hurdiss & Ola, 2021. "A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21968-w
    DOI: 10.1038/s41467-021-21968-w
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    Cited by:

    1. Timothy J. C. Tan & Zongjun Mou & Ruipeng Lei & Wenhao O. Ouyang & Meng Yuan & Ge Song & Raiees Andrabi & Ian A. Wilson & Collin Kieffer & Xinghong Dai & Kenneth A. Matreyek & Nicholas C. Wu, 2023. "High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Anahita Fathi & Christine Dahlke & Verena Krähling & Alexandra Kupke & Nisreen M. A. Okba & Matthijs P. Raadsen & Jasmin Heidepriem & Marcel A. Müller & Grigori Paris & Susan Lassen & Michael Klüver &, 2022. "Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. X. Tong & R. P. McNamara & M. J. Avendaño & E. F. Serrano & T. García-Salum & C. Pardo-Roa & H. L. Bertera & T. M. Chicz & J. Levican & E. Poblete & E. Salinas & A. Muñoz & A. Riquelme & G. Alter & R., 2023. "Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Chunyan Wang & Emma L. Hesketh & Tatiana M. Shamorkina & Wentao Li & Peter J. Franken & Dubravka Drabek & Rien Haperen & Sarah Townend & Frank J. M. Kuppeveld & Frank Grosveld & Neil A. Ranson & Joost, 2022. "Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Ching-Lin Hsieh & Sarah R. Leist & Emily Happy Miller & Ling Zhou & John M. Powers & Alexandra L. Tse & Albert Wang & Ande West & Mark R. Zweigart & Jonathan C. Schisler & Rohit K. Jangra & Kartik Cha, 2024. "Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Xandra Nuqui & Lorenzo Casalino & Ling Zhou & Mohamed Shehata & Albert Wang & Alexandra L. Tse & Anupam A. Ojha & Fiona L. Kearns & Mia A. Rosenfeld & Emily Happy Miller & Cory M. Acreman & Surl-Hee A, 2024. "Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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