Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Broad sarbecovirus neutralization by a human monoclonal antibody

Abstract

The recent emergence of SARS-CoV-2 variants of concern (VOC)1–10 and the recurrent spillovers of coronaviruses11,12 in the human population highlight the need for broadly neutralizing antibodies that are not affected by the ongoing antigenic drift and that can prevent or treat future zoonotic infections. Here, we describe a human monoclonal antibody (mAb), designated S2X259, recognizing a highly conserved cryptic receptor-binding domain (RBD) epitope and cross-reacting with spikes from all sarbecovirus clades. S2X259 broadly neutralizes spike-mediated entry of SARS-CoV-2 including the B.1.1.7, B.1.351, P.1, B.1.427/B.1.429 VOC, as well as a wide spectrum of human and potentially zoonotic sarbecoviruses through inhibition of ACE2 binding to the RBD. Furthermore, deep-mutational scanning and in vitro escape selection experiments demonstrate that S2X259 possesses an escape profile limited to the single substitution G504D. We show that prophylactic and therapeutic administration of S2X259 protects Syrian hamsters against challenge with the prototypic SARS-CoV-2 and the B.1.351 VOC, suggesting this mAb is a promising candidate for the prevention and treatment of emergent variants and zoonotic infections. Our data unveil a key antigenic site targeted by broadly-neutralizing antibodies and will guide the design of pan-sarbecovirus vaccines.

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Davide Corti or David Veesler or Matteo Samuele Pizzuto.

Supplementary information

Supplementary Tables

This file contains Supplementary Tables 1-5.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tortorici, M., Czudnochowski, N., Starr, T.N. et al. Broad sarbecovirus neutralization by a human monoclonal antibody. Nature (2021). https://doi.org/10.1038/s41586-021-03817-4

Download citation

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing