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Science
. 2020 Jun 15;eabc7424.
doi: 10.1126/science.abc7424. Online ahead of print.
Broad Neutralization of SARS-related Viruses by Human Monoclonal Antibodies
Anna Z Wec 1 , Daniel Wrapp 2 , Andrew S Herbert 3 , Daniel P Maurer 1 , Denise Haslwanter 4 , Mrunal Sakharkar 1 , Rohit K Jangra 4 , M Eugenia Dieterle 4 , Asparouh Lilov 1 , Deli Huang 5 , Longping V Tse 6 , Nicole V Johnson 2 , Ching-Lin Hsieh 2 , Nianshuang Wang 2 , Juergen H Nett 1 , Elizabeth Champney 1 , Irina Burnina 1 , Michael Brown 1 , Shu Lin 1 , Melanie Sinclair 1 , Carl Johnson 1 , Sarat Pudi 1 , Robert Bortz 3rd 4 , Ariel S Wirchnianski 4 , Ethan Laudermilch 4 , Catalina Florez 4 , J Maximilian Fels 4 , Cecilia M O'Brien 3 , Barney S Graham 7 , David Nemazee 5 , Dennis R Burton 5 8 9 10 , Ralph S Baric 6 11 , James E Voss 5 , Kartik Chandran 4 , John M Dye 3 , Jason S McLellan 2 , Laura M Walker 12
Affiliations
- PMID: 32540900
- DOI: 10.1126/science.abc7424
Abstract
Broadly protective vaccines against known and pre-emergent 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 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 non-neutralizing 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 target for the rational design of pan-sarbecovirus vaccines.