Broad betacoronavirus neutralization by a stem helix–specific human antibody

Dora Pinto, Maximilian M. Sauer, Nadine Czudnochowski, Jun Siong Low, M. Alejandra Tortorici, Michael P. Housley, Julia Noack, Alexandra C. Walls, John E. Bowen, Barbara Guarino, Laura E. Rosen, Julia di Iulio, Josipa Jerak, Hannah Kaiser, Saiful Islam, Stefano Jaconi, Nicole Sprugasci, Katja Culap, Rana Abdelnabi, Caroline FooLotte Coelmont, Istvan Bartha, Siro Bianchi, Chiara Silacci-Fregni, Jessica Bassi, Roberta Marzi, Eneida Vetti, Antonino Cassotta, Alessandro Ceschi, Paolo Ferrari, Pietro E. Cippà, Olivier Giannini, Samuele Ceruti, Christian Garzoni, Agostino Riva, Fabio Benigni, Elisabetta Cameroni, Luca Piccoli, Matteo S. Pizzuto, Megan Smithey, David Hong, Amalio Telenti, Florian A. Lempp, Johan Neyts, Colin Havenar-Daughton, Antonio Lanzavecchia, Federica Sallusto, Gyorgy Snell, Herbert W. Virgin, Martina Beltramello, Davide Corti, David Veesler

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The spillovers of betacoronaviruses in humans and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight the need for broad coronavirus countermeasures. We describe five monoclonal antibodies (mAbs) cross-reacting with the stem helix of multiple betacoronavirus spike glycoproteins isolated from COVID-19 convalescent individuals. Using structural and functional studies, we show that the mAb with the greatest breadth (S2P6) neutralizes pseudotyped viruses from three different subgenera through the inhibition of membrane fusion, and we delineate the molecular basis for its cross-reactivity. S2P6 reduces viral burden in hamsters challenged with SARS-CoV-2 through viral neutralization and Fc-mediated effector functions. Stem helix antibodies are rare, oftentimes of narrow specificity, and can acquire neutralization breadth through somatic mutations. These data provide a framework for structure-guided design of pan-betacoronavirus vaccines eliciting broad protection.

Original languageEnglish (US)
Pages (from-to)1109-1116
Number of pages8
JournalScience
Volume373
Issue number6559
DOIs
StatePublished - Sep 3 2021

ASJC Scopus subject areas

  • General

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