The race to produce vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began when the first sequence was published, and this forms the basis for vaccines currently deployed globally. Independent lineages of SARS-CoV-2 have recently been reported: UK, B.1.1.7; South Africa, B.1.351; and Brazil, P.1. These variants have multiple changes in the immunodominant spike protein that facilitates viral cell entry via the angiotensin-converting enzyme-2 (ACE2) receptor. Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape. Here, we describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor-binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K, although K417N and N501Y act together against some important antibody classes. In a number of cases, it would appear that convalescent and some vaccine serum offers limited protection against this variant.
Bibliographical noteFunding Information:
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant 2018-I2M-2-002 ) to D.I.S. and G.R.S. H.M.E.D. and J.R. are supported by the Wellcome Trust ( 101122/Z/13/Z ), Y.Z. by Cancer Research UK ( C375/A17721 ), and D.I.S. and E.E.F. by the UK Medical Research Council ( MR/N00065X/1 ). D.I.S. is a Jenner Investigator. We are grateful for a Fast grant from Fast Grants, Mercatus Center , to support the isolation of human mAbs to SARS-CoV-2 and Schmidt Futures for support of this work. G.R.S. is also supported as a Wellcome Trust Senior Investigator grant 095541/A/11/Z . This is a contribution from the UK Instruct-ERIC Centre. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (grant 090532/Z/09/Z ). Virus used for the neutralization assays was a gift from Julian Druce, Doherty Centre, Melbourne, Australia. Chanice Knight, Emily Chiplin, Ross Fothergill, and Liz Penn contributed to assays. We acknowledge Diamond Light Source for time on Beamline I03 under proposal lb27009 for COVID-19 Rapid Access. Huge thanks to the teams, especially at the Diamond Light Source and Department of Structural Biology, Oxford University, who have enabled work to continue during the pandemic. The computational aspects of this research were supported by the Wellcome Trust Core Award Grant 203141/Z/16/Z and the NIHR Oxford BRC . The Oxford Vaccine work was supported by UK Research and Innovation , Coalition for Epidemic Preparedness Innovations , National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre , and Thames Valley and South Midland’s NIHR Clinical Research Network . We thank the Oxford Protective T-cell Immunology for COVID-19 (OPTIC) Clinical team for participant sample collection and the Oxford Immunology Network COVID-19 Response T cell Consortium for laboratory support. We acknowledge the rapid sharing of the variant B.1.351, which was isolated by scientists within the National Infection Service at PHE Porton Down. This work was supported by the UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to COVID-19 in Health Workers) Consortium, the UK Coronavirus Immunology Consortium (UK-CIC), and the Huo Family Foundation . E.B. and P.K. are NIHR Senior Investigators, and P.K. is funded by WT109965MA and NIH ( U19 I082360 ). J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and is supported by NIHR Oxford Biomedical Research Centre and CIFMS. D.S. is an NIHR Academic Clinical Fellow, and S.F.L. is funded as a Wellcome Trust clinical research fellow. The views expressed in this article are those of the authors and not necessarily those of the National Health Service (NHS), the Department of Health and Social Care (DHSC), the NIHR, the Medical Research Council (MRC), or Public Health, England.
Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Publisher Copyright: © 2021 The Author(s). Published by Elsevier Inc
Citation: Zhou, Daming, et al. "Evidence of escape of SARS-CoV-2 variant B. 1.351 from natural and vaccine-induced sera." Cell 184.9 (2021): 2348-2361.
- South Africa
- receptor-binding domain