%0 Journal Article %A Anna Z. Wec %A Daniel Wrapp %A Andrew S. Herbert %A Daniel Maurer %A Denise Haslwanter %A Mrunal Sakharkar %A Rohit K. Jangra %A M. Eugenia Dieterle %A Asparouh Lilov %A Deli Huang %A Longping V. Tse %A Nicole V. Johnson %A Ching-Lin Hsieh %A Nianshuang Wang %A Juergen H. Nett %A Elizabeth Champney %A Irina Burnina %A Michael Brown %A Shu Lin %A Melanie Sinclair %A Carl Johnson %A Sarat Pudi %A Robert Bortz III %A Ariel S. Wirchnianski %A Ethan Laudermilch %A Catalina Florez %A J. Maximilian Fels %A Cecilia M. O’Brien %A Barney S. Graham %A David Nemazee %A Dennis R. Burton %A Ralph S. Baric %A James E. Voss %A Kartik Chandran %A John M. Dye %A Jason S. McLellan %A Laura M. Walker %T Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein %D 2020 %R 10.1101/2020.05.15.096511 %J bioRxiv %P 2020.05.15.096511 %X 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 StatementAZW, DPM, MS, AL, JHN, EC, IB, MB, SL, MS, CJ, SP, LMW Are employees and equity holders in Adimab LLC %U https://www.biorxiv.org/content/biorxiv/early/2020/05/15/2020.05.15.096511.full.pdf