 SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escapeTyler N. Starr,
Nadine Czudnochowski,
Zhuoming Liu,
Fabrizia Zatta,
Young-Jun Park,
Amin Addetia,
Dora Pinto,
Martina Beltramello,
Patrick Hernandez,
Allison J. Greaney,
Roberta Marzi,
William G. Glass,
Ivy Zhang,
Adam S. Dingens,
John E. Bowen,
M. Alejandra Tortorici,
Alexandra C. Walls,
Jason A. Wojcechowskyj,
Anna Marco,
Laura E. Rosen,
Jiayi Zhou,
Martin Montiel-Ruiz,
Hannah Kaiser,
Josh R. Dillen,
Heather Tucker,
Jessica Bassi,
Chiara Silacci-Fregni,
Michael P. Housley,
Julia Iulio,
Gloria Lombardo,
Maria Agostini,
Nicole Sprugasci,
Katja Culap,
Stefano Jaconi,
Marcel Meury,
Exequiel Dellota,
Rana Abdelnabi,
Shi-Yan Caroline Foo,
Elisabetta Cameroni,
Spencer Stumpf,
Tristan I. Croll,
Jay C. Nix,
Colin Havenar-Daughton,
Luca Piccoli,
Fabio Benigni,
Johan Neyts,
Amalio Telenti,
Florian A. Lempp,
Matteo S. Pizzuto,
John D. Chodera,
Christy M. Hebner,
Herbert W. Virgin,
Sean P. J. Whelan,
David Veesler,
Davide Corti (),
Jesse D. Bloom () and
Gyorgy Snell ()
Nature, 2021, vol. 597, issue 7874, 97-102 Abstract: Abstract An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape1–3, have activity against diverse sarbecoviruses4–7, and be highly protective through viral neutralization8–11 and effector functions12,13. Understanding how these properties relate to each other and vary across epitopes would aid the development of therapeutic antibodies and guide vaccine design. Here we comprehensively characterize escape, breadth and potency across a panel of SARS-CoV-2 antibodies targeting the receptor-binding domain (RBD). Despite a trade-off between in vitro neutralization potency and breadth of sarbecovirus binding, we identify neutralizing antibodies with exceptional sarbecovirus breadth and a corresponding resistance to SARS-CoV-2 escape. One of these antibodies, S2H97, binds with high affinity across all sarbecovirus clades to a cryptic epitope and prophylactically protects hamsters from viral challenge. Antibodies that target the angiotensin-converting enzyme 2 (ACE2) receptor-binding motif (RBM) typically have poor breadth and are readily escaped by mutations despite high neutralization potency. Nevertheless, we also characterize a potent RBM antibody (S2E128) with breadth across sarbecoviruses related to SARS-CoV-2 and a high barrier to viral escape. These data highlight principles underlying variation in escape, breadth and potency among antibodies that target the RBD, and identify epitopes and features to prioritize for therapeutic development against the current and potential future pandemics. Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:597:y:2021:i:7874:d:10.1038_s41586-021-03807-6 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-021-03807-6 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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