Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain

doi:10.1016/j.celrep.2021.109822

Cell Reports

Volume 37, Issue 2, 12 October 2021, 109822

https://doi.org/10.1016/j.celrep.2021.109822 Get rights and content

Under a Creative Commons license

open access

Highlights

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Neutralizing monoclonal antibodies block SARS-CoV-2 virus entry
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Reduced SARS-CoV-2 infection in mice and hamsters
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Leading antibodies unaffected by VOCs, such as B1.1.7., B.1.351, and P.1
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Cryo-EM and crystallography reveal the epitope landscape of neutralizing antibodies

Summary

Potent neutralizing monoclonal antibodies are one of the few agents currently available to treat COVID-19. SARS-CoV-2 variants of concern (VOCs) that carry multiple mutations in the viral spike protein can exhibit neutralization resistance, potentially affecting the effectiveness of some antibody-based therapeutics. Here, the generation of a diverse panel of 91 human, neutralizing monoclonal antibodies provides an in-depth structural and phenotypic definition of receptor binding domain (RBD) antigenic sites on the viral spike. These RBD antibodies ameliorate SARS-CoV-2 infection in mice and hamster models in a dose-dependent manner and in proportion to in vitro, neutralizing potency. Assessing the effect of mutations in the spike protein on antibody recognition and neutralization highlights both potent single antibodies and stereotypic classes of antibodies that are unaffected by currently circulating VOCs, such as B.1.351 and P.1. These neutralizing monoclonal antibodies and others that bind analogous epitopes represent potentially useful future anti-SARS-CoV-2 therapeutics.

Graphical abstract

Keywords

SARS-CoV-2

human antibodies

crystallography

cryo-EM

anti-viral therapeutics

mAb

Data and code availability

The structure data and the antibody sequences of the SARS-CoV-2 RBD bound to PDI 37, PDI 42, PDI 93, PDI 96, PDI 210, PDI 215, PDI 222, PDI 231, WCSL 119 and WCSL 129 are available at the PDB under accession codes 7MZF, 7MZG, 7MZJ, 7MZK, 7MZL, 7MZM, 7RR0, 7MZN, 7MZH and 7MZI respectively. Electron microscopy (EM) maps are available at the electron microscopy databank (EMDB) for SARS-CoV-2 Spike bound to PDI 93, PDI 96, PDI 210, PDI 215, PDI 222, WCSL 119 and WCSL 129 under accession codes EMDB-24647, EMDB-24643, EMDB-24642, EMDB-24644, EMDB-24648, EMDB-24645 and EMDB-24646 respectively. The EM map for PDI-222 binding the SARS-CoV-2 RBD is available under accession code EMDB-24649. This paper does not report original code. Any additional information required to reanalyse the data reported in this paper is available from the lead contact upon request.

Cited by (0)

¹³: These authors contributed equally

¹⁴: Senior author

¹⁵: Lead contact