Broad neutralization of SARS-related viruses by human monoclonal antibodies

Anna Z. Wec, Daniel Wrapp, Andrew S. Herbert, Daniel P. Maurer, Denise Haslwanter, Mrunal Sakharkar, Rohit K. Jangra, M. Eugenia Dieterle, Asparouh Lilov, Deli Huang, Longping V. Tse, Nicole V. Johnson, Ching Lin Hsieh, Nianshuang Wang, Juergen H. Nett, Elizabeth Champney, Irina Burnina, Michael Brown, Shu Lin, Melanie SinclairCarl Johnson, Sarat Pudi, Robert Bortz, Ariel S. Wirchnianski, Ethan Laudermilch, Catalina Florez, J. Maximilian Fels, Cecilia M. O'Brien, Barney S. Graham, David Nemazee, Dennis R. Burton, Ralph S. Baric, James E. Voss, Kartik Chandran, John M. Dye, Jason S. McLellan, Laura M. Walker

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

Broadly protective vaccines against known and preemergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent severe acute respiratory syndrome (SARS) donor and identified 200 SARS coronavirus 2 (SARS-CoV-2) binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of preexisting memory B cells elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.

Original languageEnglish (US)
Pages (from-to)731-736
Number of pages6
JournalScience
Volume369
Issue number6504
DOIs
StatePublished - Aug 7 2020

ASJC Scopus subject areas

  • General

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