Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

The CITIID-NIHR BioResource COVID-19 Collaboration; The COVID-19 Genomics UK (COG-UK) Consortium

doi:10.1038/s41586-021-03412-7

Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

The CITIID-NIHR BioResource COVID-19 Collaboration
, The COVID-19 Genomics UK (COG-UK) Consortium

Cambridge Institute of Therapeutic Immunology & amp; Infectious Disease
Department of Medicine
University College London
a subsidiary of Vir Biotechnology
University of Washington School of Medicine
Clinica Luganese Moncucco
University Hospital "Luigi Sacco"
Wellcome Sanger Centre
University Hospital Basel
Botnar Research Centre for Child Health
University of Kent
Department of Haematology
Addenbrookes Hospital
Heart and Lung Research Institute
Papworth Hospital
University of Cambridge
Cardiff University School of Medicine
Cambridge Institute for Medical Research
Department of Veterinary Medicine
Cancer Research UK Cambridge Institute
The Rosie Maternity Hospital
University of Portsmouth
Wellcome Trust Genome Campus
University of Birmingham
University of Colorado School of Medicine
Fulbourn Hospital
Murdoch University
Department of Public Health and Primary Care
NIHR Cambridge Clinical Research Facility
NIHR Cambridge Bioresource
UNAM
Public Health Wales
University of Oxford
King's College London
University of Brighton
Guys and St Thomas' NHS Foundation Trust
Cambridge University Hospitals NHS Foundation Trust
University Hospital Southampton NHS Foundation Trust
University of Southampton, Faculty of Medicine
University of Southampton
St Thomas' Hospital
Forster Green Hospital
Queen's University of Belfast
University of Nottingham
East Kent Hospitals University NHS Foundation Trust
Ellison Building
University of Oxford
Public Health England
MRC-University of Glasgow Centre for Virus Research
University of Sheffield
Portsmouth Hospitals University NHS Trust
NHS Lothian
University of Edinburgh
Quadram Institute Bioscience
University of East Anglia
Public Health Scotland
East Birmingham Hospital
Oxford University Hospitals NHS Foundation Trust
Brighton and Sussex University Hospitals
University of Warwick
University of Liverpool School of Medicine
Imperial College London
Newcastle upon Tyne NHS Hospitals Foundation Trust
University Hospitals Coventry and Warwickshire NHS Trust
University of Exeter
Betsi Cadwaladr University Health Board
UCL Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust
Cardiff and Vale University Health Board
Gloucestershire Hospitals NHS Foundation Trust
Wye valley NHS Trust
Sandwell and West Birmingham NHS Trust
Norfolk and Norwich University Hospitals NHS Foundation Trust
Royal Devon and Exeter National Health Service Foundation Trust
Barking, Havering and Redbridge University Hospitals NHS Trust
Queen Elizabeth Hospital Birmingham
Kettering General Hospital
University Hospitals of Leicester NHS Trust
Imperial College Healthcare NHS Trust
North West London Pathology
Royal Free NHS Trust
South Tees Hospitals NHS Foundation Trust
North Cumbria Integrated Care NHS Foundation Trust
North Tees and Hartlepool NHS Foundation Trust
County Durham and Darlington NHS Foundation Trust
Queen's Medical Centre
Northern Lincolnshire & amp; Goole NHS Foundation Trust
Basingstoke Hospital
University of Surrey
Swansea University
Ministry of Health Colombo
Liverpool Clinical Laboratories
Imperial College London
Health Data Research UK
Hampshire Hospitals NHS Foundation Trust
Public Health
London School of Hygiene and Tropical Medicine
NHS Greater Glasgow and Clyde
Leeds Teaching Hospitals NHS Trust
University Hospital of South Manchester
Health Services Laboratories
Maidstone and Tunbridge Wells NHS Trust
Gateshead Health NHS Foundation Trust
Norfolk County Council
Ipswich Hospital NHS Trust
Princess Alexandra Hospital
Sheffield Teaching Hospitals NHS Foundation Trust
University of Glasgow, G11 6NT
University of Glasgow
University of KwaZulu–Natal
Africa Health Research Institute

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

544 Citations (Scopus)

Abstract

Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant¹, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b2². We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

Original language	English
Pages (from-to)	136-141
Number of pages	6
Journal	Nature
Volume	593
Issue number	7857
DOIs	https://doi.org/10.1038/s41586-021-03412-7
Publication status	Published - 6 May 2021
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/s41586-021-03412-7

Cite this

@article{63dd28cb9f0f4062bce23754b31f6312,

title = "Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies",

abstract = "Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.",

author = "\{The CITIID-NIHR BioResource COVID-19 Collaboration\} and \{The COVID-19 Genomics UK (COG-UK) Consortium\} and Collier, \{Dami A.\} and \{De Marco\}, Anna and Ferreira, \{Isabella A.T.M.\} and Bo Meng and Datir, \{Rawlings P.\} and Walls, \{Alexandra C.\} and Kemp, \{Steven A.\} and Jessica Bassi and Dora Pinto and Chiara Silacci-Fregni and Siro Bianchi and Tortorici, \{M. Alejandra\} and John Bowen and Katja Culap and Stefano Jaconi and Elisabetta Cameroni and Gyorgy Snell and Pizzuto, \{Matteo S.\} and Pellanda, \{Alessandra Franzetti\} and Christian Garzoni and Agostino Riva and Stephen Baker and Gordon Dougan and Christoph Hess and Nathalie Kingston and Lehner, \{Paul J.\} and Lyons, \{Paul A.\} and Matheson, \{Nicholas J.\} and Owehand, \{Willem H.\} and Caroline Saunders and Charlotte Summers and Thaventhiran, \{James E.D.\} and Mark Toshner and Weekes, \{Michael P.\} and Ashlea Bucke and Jo Calder and Laura Canna and Jason Domingo and Anne Elmer and Stewart Fuller and Julie Harris and Sarah Hewitt and Jane Kennet and Sherly Jose and Jenny Kourampa and Anne Meadows and Criona O{\textquoteright}Brien and Jane Price and Cherry Publico and Rebecca Rastall and Carla Ribeiro and Jane Rowlands and Valentina Ruffolo and Hugo Tordesillas and Ben Bullman and Dunmore, \{Benjamin J.\} and Stuart Fawke and Stefan Gr{\"a}f and Josh Hodgson and Christopher Huang and Kelvin Hunter and Emma Jones and Ekaterina Legchenko and Cecilia Matara and Jennifer Martin and Federica Mescia and Ciara O{\textquoteright}Donnell and Linda Pointon and Nicole Pond and Joy Shih and Rachel Sutcliffe and Tobias Tilly and Carmen Treacy and Zhen Tong and Jennifer Wood and Marta Wylot and Laura Bergamaschi and Ariana Betancourt and Georgie Bower and Chiara Cossetti and \{De Sa\}, Aloka and Madeline Epping and Richard Grenfell and Andrew Hinch and Oisin Huhn and Sarah Jackson and Isobel Jarvis and Daniel Lewis and Joe Marsden and Francesca Nice and Georgina Okecha and Ommar Omarjee and Marianne Perera and Nathan Richoz and Veronika Romashova and Yarkoni, \{Natalia Savinykh\} and Rahul Sharma and Luca Stefanucci and Jonathan Stephens and Dorman, \{Matthew J.\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = may,

day = "6",

doi = "10.1038/s41586-021-03412-7",

language = "English",

volume = "593",

pages = "136--141",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7857",

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TY - JOUR

T1 - Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

AU - The CITIID-NIHR BioResource COVID-19 Collaboration

AU - The COVID-19 Genomics UK (COG-UK) Consortium

AU - Collier, Dami A.

AU - De Marco, Anna

AU - Ferreira, Isabella A.T.M.

AU - Meng, Bo

AU - Datir, Rawlings P.

AU - Walls, Alexandra C.

AU - Kemp, Steven A.

AU - Bassi, Jessica

AU - Pinto, Dora

AU - Silacci-Fregni, Chiara

AU - Bianchi, Siro

AU - Tortorici, M. Alejandra

AU - Bowen, John

AU - Culap, Katja

AU - Jaconi, Stefano

AU - Cameroni, Elisabetta

AU - Snell, Gyorgy

AU - Pizzuto, Matteo S.

AU - Pellanda, Alessandra Franzetti

AU - Garzoni, Christian

AU - Riva, Agostino

AU - Baker, Stephen

AU - Dougan, Gordon

AU - Hess, Christoph

AU - Kingston, Nathalie

AU - Lehner, Paul J.

AU - Lyons, Paul A.

AU - Matheson, Nicholas J.

AU - Owehand, Willem H.

AU - Saunders, Caroline

AU - Summers, Charlotte

AU - Thaventhiran, James E.D.

AU - Toshner, Mark

AU - Weekes, Michael P.

AU - Bucke, Ashlea

AU - Calder, Jo

AU - Canna, Laura

AU - Domingo, Jason

AU - Elmer, Anne

AU - Fuller, Stewart

AU - Harris, Julie

AU - Hewitt, Sarah

AU - Kennet, Jane

AU - Jose, Sherly

AU - Kourampa, Jenny

AU - Meadows, Anne

AU - O’Brien, Criona

AU - Price, Jane

AU - Publico, Cherry

AU - Rastall, Rebecca

AU - Ribeiro, Carla

AU - Rowlands, Jane

AU - Ruffolo, Valentina

AU - Tordesillas, Hugo

AU - Bullman, Ben

AU - Dunmore, Benjamin J.

AU - Fawke, Stuart

AU - Gräf, Stefan

AU - Hodgson, Josh

AU - Huang, Christopher

AU - Hunter, Kelvin

AU - Jones, Emma

AU - Legchenko, Ekaterina

AU - Matara, Cecilia

AU - Martin, Jennifer

AU - Mescia, Federica

AU - O’Donnell, Ciara

AU - Pointon, Linda

AU - Pond, Nicole

AU - Shih, Joy

AU - Sutcliffe, Rachel

AU - Tilly, Tobias

AU - Treacy, Carmen

AU - Tong, Zhen

AU - Wood, Jennifer

AU - Wylot, Marta

AU - Bergamaschi, Laura

AU - Betancourt, Ariana

AU - Bower, Georgie

AU - Cossetti, Chiara

AU - De Sa, Aloka

AU - Epping, Madeline

AU - Grenfell, Richard

AU - Hinch, Andrew

AU - Huhn, Oisin

AU - Jackson, Sarah

AU - Jarvis, Isobel

AU - Lewis, Daniel

AU - Marsden, Joe

AU - Nice, Francesca

AU - Okecha, Georgina

AU - Omarjee, Ommar

AU - Perera, Marianne

AU - Richoz, Nathan

AU - Romashova, Veronika

AU - Yarkoni, Natalia Savinykh

AU - Sharma, Rahul

AU - Stefanucci, Luca

AU - Stephens, Jonathan

AU - Dorman, Matthew J.

PY - 2021/5/6

Y1 - 2021/5/6

N2 - Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

AB - Transmission of SARS-CoV-2 is uncontrolled in many parts of the world; control is compounded in some areas by the higher transmission potential of the B.1.1.7 variant1, which has now been reported in 94 countries. It is unclear whether the response of the virus to vaccines against SARS-CoV-2 on the basis of the prototypic strain will be affected by the mutations found in B.1.1.7. Here we assess the immune responses of individuals after vaccination with the mRNA-based vaccine BNT162b22. We measured neutralizing antibody responses after the first and second immunizations using pseudoviruses that expressed the wild-type spike protein or a mutated spike protein that contained the eight amino acid changes found in the B.1.1.7 variant. The sera from individuals who received the vaccine exhibited a broad range of neutralizing titres against the wild-type pseudoviruses that were modestly reduced against the B.1.1.7 variant. This reduction was also evident in sera from some patients who had recovered from COVID-19. Decreased neutralization of the B.1.1.7 variant was also observed for monoclonal antibodies that target the N-terminal domain (9 out of 10) and the receptor-binding motif (5 out of 31), but not for monoclonal antibodies that recognize the receptor-binding domain that bind outside the receptor-binding motif. Introduction of the mutation that encodes the E484K substitution in the B.1.1.7 background to reflect a newly emerged variant of concern (VOC 202102/02) led to a more-substantial loss of neutralizing activity by vaccine-elicited antibodies and monoclonal antibodies (19 out of 31) compared with the loss of neutralizing activity conferred by the mutations in B.1.1.7 alone. The emergence of the E484K substitution in a B.1.1.7 background represents a threat to the efficacy of the BNT162b2 vaccine.

UR - https://www.scopus.com/pages/publications/85102509491

U2 - 10.1038/s41586-021-03412-7

DO - 10.1038/s41586-021-03412-7

M3 - Article

SN - 0028-0836

VL - 593

SP - 136

EP - 141

JO - Nature

JF - Nature

IS - 7857

ER -

Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Abstract

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