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,
Maria 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 S Graham,
David Nemazee,
Dennis R. Burton,
Ralph S. 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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