Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

Piyada Supasa, Daming Zhou, Wanwisa Dejnirattisai, Chang Liu, Alexander J. Mentzer, Helen M. Ginn, Yuguang Zhao, Helen M.E. Duyvesteyn, Rungtiwa Nutalai, Aekkachai Tuekprakhon, Beibei Wang, Guido C. Paesen, Jose Slon-Campos, César López-Camacho, Bassam Hallis, Naomi Coombes, Kevin R. Bewley, Sue Charlton, Thomas S. Walter, Eleanor BarnesSusanna J. Dunachie, Donal Skelly, Sheila F. Lumley, Natalie Baker, Imam Shaik, Holly E. Humphries, Kerry Godwin, Nick Gent, Alex Sienkiewicz, Christina Dold, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Paul Klenerman, Derrick Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-Rammerstorfer, Sarah Gilbert, David R. Hall, Mark A. Williams, Neil G. Paterson, William James, Miles Carroll, Elizabeth E. Fry, Juthathip Mongkolsapaya*, Jingshan Ren, David I. Stuart, Gavin R. Screaton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

208 Citations (Scopus)

Abstract

SARS-CoV-2 has caused over 2 million deaths in little over a year. Vaccines are being deployed at scale, aiming to generate responses against the virus spike. The scale of the pandemic and error-prone virus replication is leading to the appearance of mutant viruses and potentially escape from antibody responses. Variant B.1.1.7, now dominant in the UK, with increased transmission, harbors 9 amino acid changes in the spike, including N501Y in the ACE2 interacting surface. We examine the ability of B.1.1.7 to evade antibody responses elicited by natural SARS-CoV-2 infection or vaccination. We map the impact of N501Y by structure/function analysis of a large panel of well-characterized monoclonal antibodies. B.1.1.7 is harder to neutralize than parental virus, compromising neutralization by some members of a major class of public antibodies through light-chain contacts with residue 501. However, widespread escape from monoclonal antibodies or antibody responses generated by natural infection or vaccination was not observed.

Original languageEnglish
Pages (from-to)2201-+
Number of pages18
JournalCell
Volume184
Issue number8
DOIs
Publication statusPublished - 15 Apr 2021

Bibliographical note

Funding Information:
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002 ) to D.I.S. and G.R.S. H.M.E.D. and J. Ren 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 . The National Institute for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. We are also grateful for a Fast Grant from Fast Grants, Mercatus Center to support the isolation of human monoclonal antibodies to SARS-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 ). The 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 that have enabled work to continue during the pandemic. The computational aspects of this research were supported by the Wellcome Trust Core Award grant number 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 the 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.1.1.7, 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 ). S.F.L. is a Wellcome Trust Clinical Research Fellow. J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. D.S. is an NIHR Academic Clinical 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 National Institutes for Health Research (NIHR), the Medical Research Council (MRC) or Public Health, England.

Funding Information:
This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (grant number: 2018-I2M-2-002) to D.I.S. and G.R.S. H.M.E.D. and J. Ren 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. The National Institute for Health Research Biomedical Research Centre Funding Scheme supports G.R.S. We are also grateful for a Fast Grant from Fast Grants, Mercatus Center to support the isolation of human monoclonal antibodies to SARS-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). The 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 that have enabled work to continue during the pandemic. The computational aspects of this research were supported by the Wellcome Trust Core Award grant number 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 the 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.1.1.7, 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). S.F.L. is a Wellcome Trust Clinical Research Fellow. J.C.K. is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centre and CIFMS. D.S. is an NIHR Academic Clinical 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 National Institutes for Health Research (NIHR), the Medical Research Council (MRC) or Public Health, England. D.Z. performed interaction analyses. T.S.W. performed biophysical analyses. Y.Z. D.Z. and J. Ren performed sample preparation for and crystallographic experiments and processed the data. D.R.H. M.A.W. and N.G.P. assisted with X-ray diffraction data collection. J. Ren refined the structures and together with E.E.F. H.M.E.D. and D.I.S. analyzed the results. G.R.S. J.M. P.S. Y.Z. G.C.P. and C.L. prepared the spike construct and antibodies, and W.D. performed neutralization assays with B.W. R.N. A.T. J.S.-C. and C.L.-C. B.H. N.C. K.R.B. S.C. N.B. I.S. H.E.H. K.G. N.G. and A.S. provided B.1.1.7 virus and contributed to experimental design. D.C. and W.J. provided materials. H.M.G. wrote the software for the epitope mapping and performed mapping and cluster analysis, including of sequences. A.J.M. S.F.L. E.B. S.J.D. D.S. C.D. R.L. T.D. A.J.P. J.C.K. P.K. M.W.C. T.L. S.B. A.F. M.B. S.B.-R. E.C. and S.G. assisted with patient samples and vaccine trials. E.B. M.C. S.J.D. P.K. and D.S. conceived the study of vaccinated healthcare workers and oversaw the OPTIC Healthcare Worker study and sample collection/processing. G.R.S. and D.I.S. wrote the initial manuscript draft with other authors providing editorial comments. All authors read and approved the manuscript. G.R.S. sits on the GSK Vaccines Scientific Advisory Board. Oxford University holds intellectual property related to the Oxford-AstraZeneca vaccine. A.J.P. is Chair of UK Department Health and Social Care's (DHSC) Joint Committee on Vaccination & Immunisation (JCVI) but does not participate in the JCVI COVID19 committee and is a member of the WHO's SAGE. S.G. is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and consultant to Vaccitech. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. The University of Oxford has protected intellectual property disclosed in this publication.

Publisher Copyright:
© 2021 The Authors

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • B.1.1.7
  • IGHV3-53
  • Kent
  • SARS-CoV-2
  • antibody
  • escape
  • neutralization
  • variant
  • SYSTEM
  • ACE2
  • RECEPTOR
  • EXPRESSION

Fingerprint

Dive into the research topics of 'Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera'. Together they form a unique fingerprint.

Cite this