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

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, Olalekan Daramola, Frank Grosveld, Frank J. M. Kuppeveld, Bart L. Haagmans, Luis Enjuanes, Dubravka Drabek and Berend-Jan Bosch ()
Additional contact information
Chunyan Wang: Utrecht University
Rien Haperen: Erasmus Medical Center
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
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
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
Berend-Jan Bosch: Utrecht University

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-21968-w

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