Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein
By
Anna Z. Wec,
Daniel Wrapp,
Andrew S Herbert,
Daniel 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 Sinclair,
Carl Johnson,
Sarat Pudi,
Robert Bortz,
Ariel S. Wirchnianski,
Ethan Laudermilch,
Catalina Florez,
J. Maximilian Fels,
Cecilia M. O’Brien,
Barney Graham,
David Nemazee,
Dennis R. Burton,
Ralph Baric,
James E. Voss,
Kartik Chandran,
John M Dye,
Jason S McLellan,
Laura M Walker
Posted 15 May 2020
bioRxiv DOI: 10.1101/2020.05.15.096511
Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) 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 new target for the rational design of pan-sarbecovirus vaccines. ### Competing Interest Statement AZW, DPM, MS, AL, JHN, EC, IB, MB, SL, MS, CJ, SP, LMW Are employees and equity holders in Adimab LLC
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