Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

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 3rd; 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

doi:10.1101/2020.05.15.096511

Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

bioRxiv [Preprint]. 2020 May 16:2020.05.15.096511. doi: 10.1101/2020.05.15.096511.

Authors

Anna Z Wec¹, Daniel Wrapp², Andrew S Herbert³, Daniel Maurer¹, Denise Haslwanter⁴, Mrunal Sakharkar¹, Rohit K Jangra⁴, M Eugenia Dieterle⁴, Asparouh Lilov¹, Deli Huang⁵, Longping V Tse⁶, Nicole V Johnson², Ching-Lin Hsieh², Nianshuang Wang², Juergen H Nett¹, Elizabeth Champney¹, Irina Burnina¹, Michael Brown¹, Shu Lin¹, Melanie Sinclair¹, Carl Johnson¹, Sarat Pudi¹, Robert Bortz 3rd⁴, Ariel S Wirchnianski⁴, Ethan Laudermilch⁴, Catalina Florez⁴, J Maximilian Fels⁴, Cecilia M O'Brien³, Barney S Graham^{1

2

3

4

5

6

7

8

9

10

11}, David Nemazee⁵, Dennis R Burton^{7

8

9

10}, Ralph S Baric^{6

11}, James E Voss⁵, Kartik Chandran⁴, John M Dye³, Jason S McLellan², Laura M Walker¹

Affiliations

¹ Adimab LLC, Lebanon, NH 03766, USA.
² Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
³ U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
⁴ Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY, USA.
⁵ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁶ Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁷ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁸ IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁹ Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
¹⁰ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard.
¹¹ Departments of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

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.

Publication types

Preprint

Abstract

Publication types

Grants and funding