The antigenic anatomy of SARS-CoV-2 receptor binding domain
Wanwisa Dejnirattisai(Centre for Human Genetics), Daming Zhou(Centre for Human Genetics), Helen M. Ginn(Diamond Light Source), Helen M. E. Duyvesteyn(Centre for Human Genetics), Piyada Supasa(Centre for Human Genetics), James Brett Case(Washington University in St. Louis), Yuguang Zhao(Centre for Human Genetics), Thomas S. Walter(Centre for Human Genetics), Alexander J. Mentzer(Centre for Human Genetics), Chang Liu(Centre for Human Genetics), Beibei Wang(Centre for Human Genetics), Guido C. Paesen(Centre for Human Genetics), Jose Slon-Campos(Centre for Human Genetics), César López‐Camacho(Centre for Human Genetics), Natasha M. Kafai(Washington University in St. Louis), Adam L. Bailey(Washington University in St. Louis), Rita E. Chen(Washington University in St. Louis), Baoling Ying(Washington University in St. Louis), Craig Thompson(University of Oxford), Jai S. Bolton(University of Oxford), Alex Fyfe(University of Oxford), Sunetra Gupta(University of Oxford), Tiong Kit Tan(University of Oxford), Javier Gilbert‐Jaramillo(University of Oxford), William James(University of Oxford), Michael L. Knight(University of Oxford), Miles W. Carroll(Centre for Human Genetics), Donal Skelly(University of Oxford), Christina Dold(University of Oxford), Yanchun Peng(University of Oxford), Robert H. Levin(Worthing Hospital), Tao Dong(University of Oxford), Andrew J. Pollard(University of Oxford), Julian C. Knight(Centre for Human Genetics), Paul Klenerman(University of Oxford), Nigel Temperton(Medway School of Pharmacy), David R. Hall(Diamond Light Source), Mark A. Williams(Diamond Light Source), Neil G. Paterson(Diamond Light Source), F.K.R. Bertram(Diamond Light Source), C. Alistair Siebert(Diamond Light Source), Daniel K. Clare(Diamond Light Source), Andrew Howe(Diamond Light Source), Julika Radecke(Diamond Light Source), Yun Song(Diamond Light Source), Alain Townsend(University of Oxford), Kuan-Ying A. Huang(Chang Gung University), Elizabeth E. Fry(Centre for Human Genetics), Juthathip Mongkolsapaya(Siriraj Hospital), Michael Diamond(Washington University in St. Louis), Jingshan Ren(Centre for Human Genetics), David I. Stuart(Centre for Human Genetics), Gavin Screaton(Centre for Human Genetics)
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Abstract
< 0.1 μg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.
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