Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Daming Zhou; Wanwisa Dejnirattisai; Piyada Supasa; Chang Liu; Alexander J. Mentzer; Helen M. Ginn; Yuguang Zhao; Helen M.E. Duyvesteyn; Aekkachai Tuekprakhon; Rungtiwa Nutalai; Beibei Wang; Guido C. Paesen; Cesar Lopez-Camacho; Jose Slon-Campos; Bassam Hallis; Naomi Coombes; Kevin Bewley; Sue Charlton; Thomas S. Walter; Donal Skelly; Sheila F. Lumley; Christina Dold; Robert Levin; Tao Dong; Andrew J. Pollard; Julian C. Knight; Derrick Crook; Teresa Lambe; Elizabeth Clutterbuck; Sagida Bibi; Amy Flaxman; Mustapha Bittaye; Sandra Belij-Rammerstorfer; Sarah Gilbert; William James; Miles Carroll; Paul Klenerman; Eleanor Barnes; Susanna J. Dunachie; Elizabeth E. Fry; Juthathip Mongkolsapaya; Jingshan Ren; David I. Stuart; Gavin R. Screaton

doi:10.1016/j.cell.2021.02.037

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Daming Zhou, Wanwisa Dejnirattisai, Piyada Supasa, Chang Liu, Alexander J. Mentzer, Helen M. Ginn, Yuguang Zhao, Helen M.E. Duyvesteyn, Aekkachai Tuekprakhon, Rungtiwa Nutalai, Beibei Wang, Guido C. Paesen, Cesar Lopez-Camacho, Jose Slon-Campos, Bassam Hallis, Naomi Coombes, Kevin Bewley, Sue Charlton, Thomas S. Walter, Donal SkellySheila F. Lumley, Christina Dold, Robert Levin, Tao Dong, Andrew J. Pollard, Julian C. Knight, Derrick Crook, Teresa Lambe, Elizabeth Clutterbuck, Sagida Bibi, Amy Flaxman, Mustapha Bittaye, Sandra Belij-Rammerstorfer, Sarah Gilbert, William James, Miles Carroll, Paul Klenerman, Eleanor Barnes, Susanna J. Dunachie, Elizabeth E. Fry, Juthathip Mongkolsapaya^*, Jingshan Ren, David I. Stuart, Gavin R. Screaton

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

767 Citations (Scopus)

48 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	2348-2361.e6
Journal	Cell
Volume	184
Issue number	9
Early online date	23 Feb 2021
DOIs	https://doi.org/10.1016/j.cell.2021.02.037
Publication status	Published - 29 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 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.

DOI: https://doi.org/10.1016/j.cell.2021.02.037

Keywords

ACE2
B.1.351
SARS-CoV-2
South Africa
antibody
escape
neutralization
receptor-binding domain
vaccine
variant

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cell.2021.02.037Licence: CC BY

Zhou2021EvidenceOfEscapeofSARS-CoV-2VariantB.1.351CellFinal published version, 5 MBLicence: CC BY

Cite this

Zhou, D., Dejnirattisai, W., Supasa, P., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Tuekprakhon, A., Nutalai, R., Wang, B., Paesen, G. C., Lopez-Camacho, C., Slon-Campos, J., Hallis, B., Coombes, N., Bewley, K., Charlton, S., Walter, T. S., ... Screaton, G. R. (2021). Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera. Cell, 184(9), 2348-2361.e6. https://doi.org/10.1016/j.cell.2021.02.037

@article{bee15edc8b5e4a20ae0a9c43450904b7,

title = "Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera",

abstract = "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.",

keywords = "ACE2, B.1.351, SARS-CoV-2, South Africa, antibody, escape, neutralization, receptor-binding domain, vaccine, variant",

author = "Daming Zhou and Wanwisa Dejnirattisai and Piyada Supasa and Chang Liu and Mentzer, {Alexander J.} and Ginn, {Helen M.} and Yuguang Zhao and Duyvesteyn, {Helen M.E.} and Aekkachai Tuekprakhon and Rungtiwa Nutalai and Beibei Wang and Paesen, {Guido C.} and Cesar Lopez-Camacho and Jose Slon-Campos and Bassam Hallis and Naomi Coombes and Kevin Bewley and Sue Charlton and Walter, {Thomas S.} and Donal Skelly and Lumley, {Sheila F.} and Christina Dold and Robert Levin and Tao Dong and Pollard, {Andrew J.} and Knight, {Julian C.} and Derrick Crook and Teresa Lambe and Elizabeth Clutterbuck and Sagida Bibi and Amy Flaxman and Mustapha Bittaye and Sandra Belij-Rammerstorfer and Sarah Gilbert and William James and Miles Carroll and Paul Klenerman and Eleanor Barnes and Dunachie, {Susanna J.} and Fry, {Elizabeth E.} and Juthathip Mongkolsapaya and Jingshan Ren and Stuart, {David I.} and Screaton, {Gavin R.}",

note = "Funding 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{\textquoteright}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: {\textcopyright} 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. DOI: https://doi.org/10.1016/j.cell.2021.02.037 ",

year = "2021",

month = apr,

day = "29",

doi = "10.1016/j.cell.2021.02.037",

language = "English",

volume = "184",

pages = "2348--2361.e6",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "9",

}

Zhou, D, Dejnirattisai, W, Supasa, P, Liu, C, Mentzer, AJ, Ginn, HM, Zhao, Y, Duyvesteyn, HME, Tuekprakhon, A, Nutalai, R, Wang, B, Paesen, GC, Lopez-Camacho, C, Slon-Campos, J, Hallis, B , Coombes, N , Bewley, K , Charlton, S, Walter, TS, Skelly, D, Lumley, SF, Dold, C, Levin, R, Dong, T, Pollard, AJ, Knight, JC, Crook, D, Lambe, T, Clutterbuck, E, Bibi, S, Flaxman, A, Bittaye, M, Belij-Rammerstorfer, S, Gilbert, S, James, W, Carroll, M, Klenerman, P, Barnes, E, Dunachie, SJ, Fry, EE, Mongkolsapaya, J, Ren, J, Stuart, DI & Screaton, GR 2021, 'Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera', Cell, vol. 184, no. 9, pp. 2348-2361.e6. https://doi.org/10.1016/j.cell.2021.02.037

TY - JOUR

T1 - Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

AU - Zhou, Daming

AU - Dejnirattisai, Wanwisa

AU - Supasa, Piyada

AU - Liu, Chang

AU - Mentzer, Alexander J.

AU - Ginn, Helen M.

AU - Zhao, Yuguang

AU - Duyvesteyn, Helen M.E.

AU - Tuekprakhon, Aekkachai

AU - Nutalai, Rungtiwa

AU - Wang, Beibei

AU - Paesen, Guido C.

AU - Lopez-Camacho, Cesar

AU - Slon-Campos, Jose

AU - Hallis, Bassam

AU - Coombes, Naomi

AU - Bewley, Kevin

AU - Charlton, Sue

AU - Walter, Thomas S.

AU - Skelly, Donal

AU - Lumley, Sheila F.

AU - Dold, Christina

AU - Levin, Robert

AU - Dong, Tao

AU - Pollard, Andrew J.

AU - Knight, Julian C.

AU - Crook, Derrick

AU - Lambe, Teresa

AU - Clutterbuck, Elizabeth

AU - Bibi, Sagida

AU - Flaxman, Amy

AU - Bittaye, Mustapha

AU - Belij-Rammerstorfer, Sandra

AU - Gilbert, Sarah

AU - James, William

AU - Carroll, Miles

AU - Klenerman, Paul

AU - Barnes, Eleanor

AU - Dunachie, Susanna J.

AU - Fry, Elizabeth E.

AU - Mongkolsapaya, Juthathip

AU - Ren, Jingshan

AU - Stuart, David I.

AU - Screaton, Gavin R.

N1 - Funding 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. DOI: https://doi.org/10.1016/j.cell.2021.02.037

PY - 2021/4/29

Y1 - 2021/4/29

N2 - 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.

AB - 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.

KW - ACE2

KW - B.1.351

KW - SARS-CoV-2

KW - South Africa

KW - antibody

KW - escape

KW - neutralization

KW - receptor-binding domain

KW - vaccine

KW - variant

UR - http://www.scopus.com/inward/record.url?scp=85102634643&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2021.02.037

DO - 10.1016/j.cell.2021.02.037

M3 - Article

AN - SCOPUS:85102634643

SN - 0092-8674

VL - 184

SP - 2348-2361.e6

JO - Cell

JF - Cell

IS - 9

ER -

Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this