Isolation of cross-reactive monoclonal antibodies against divergent human coronaviruses that delineate a conserved and vulnerable site on the spike protein
Open accessAbstract
The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry. As such, it is an attractive target for the development of protective antibodies and vaccines. Here we describe two human monoclonal antibodies, 1.6C7 and 28D9, that display a remarkable cross-reactivity against distinct species from three Betacoronavirus subgenera, capable of binding the spike proteins of SARS-CoV and SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both antibodies, derived from immunized transgenic mice carrying a human immunoglobulin repertoire, blocked MERS-CoV infection in cells, whereas 28D9 also showed weak cross-neutralizing potential against HCoV-OC43, SARS-CoV and SARS-CoV-2 in a neutralization-sensitive virus pseudotyping system, but not against authentic virus. Both cross-reactive monoclonal antibodies were found to target the stem helix in the spike protein S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle, that is antibody-accessible. We demonstrate that administration of these antibodies in mice protects from a lethal MERS-CoV challenge in both prophylactic and/or therapeutic models. Collectively, these antibodies delineate a conserved, immunogenic and vulnerabe site on the spike protein which spurs the development of broad-range diagnostic, preventive and therapeutic measures against coronaviruses.
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Neutralizing mAbs that bind regions of the viral spike have also been identified.
“Neutralizing mAbs that bind regions of the viral spike have also been identified (24, 33, 38–42).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [42]
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References 71 · Cited by 15
Research works printed but not linked: 1
- Brouwer, P. et al. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. bioRxiv (2020).
- Authors
- Wang, C., van Haperen, R., Gutiérrez-Álvarez, J., Li, W., Okba, N. M. A., Albulescu, I., Widjaja, I., van Dieren, B., Fernandez-Delgado, R., Sola, I., Hurdiss, D. L., Daramola, O., Grosveld, F., van Kuppeveld, F. J. M., Haagmans, B. L., Enjuanes, L., Drabek, D., & Bosch, B.-J.
- Affiliations
- Utrecht University (NL)
- Erasmus MC (NL)
- Consejo Superior de Investigaciones Científicas (ES)
- AstraZeneca (United Kingdom) (GB)
- Corresponding author
- Bosch, Berend-Jan
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2020-10-20
- OpenAlex
- W3093534469
- Cited by
- 15
- References
- 71
- Citations by year
- 2022: 3 · 2021: 6 · 2020: 6
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
- Funders
- University of Bern
- Universiteit Utrecht
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- monoclonal antibodies, coronavirus spike protein, cross-reactivity, SARS-CoV-2, MERS-CoV, SARS-CoV, HCoV-OC43, Betacoronavirus, neutralizing antibodies, antibody-mediated protection
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