Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies
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 variant
1, 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 BNT162b2
2. 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.
136-141
Saeed, Kordo
87cb67e5-71e8-4759-bf23-2ea00ebd8b39
Prieto, Jacqui
47dd42cd-35d5-4ece-8fc6-fdb8fe1f01cc
Silveira, Siona
4e878a61-a0e9-4fe0-8061-5d056723d5e8
Wilson-Davies, Eleri
d00864cd-4409-4a8e-831c-464c9cebe7ee
Mahanama, Adhyana
d3c953b5-3fe2-4c76-b9cf-15292168e9f2
Samaraweera, Buddhini
71f12837-4e00-4ba7-ae37-c9db848ee214
Jeremiah, Sarah
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The COVID-19 Genomics UK (COG-UK) Consortium
6 May 2021
Saeed, Kordo
87cb67e5-71e8-4759-bf23-2ea00ebd8b39
Prieto, Jacqui
47dd42cd-35d5-4ece-8fc6-fdb8fe1f01cc
Silveira, Siona
4e878a61-a0e9-4fe0-8061-5d056723d5e8
Wilson-Davies, Eleri
d00864cd-4409-4a8e-831c-464c9cebe7ee
Mahanama, Adhyana
d3c953b5-3fe2-4c76-b9cf-15292168e9f2
Samaraweera, Buddhini
71f12837-4e00-4ba7-ae37-c9db848ee214
Jeremiah, Sarah
0abed577-ff65-4fdb-885b-8aaa563b362f
The COVID-19 Genomics UK (COG-UK) Consortium
(2021)
Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies.
Nature, 593 (7857), .
(doi:10.1038/s41586-021-03412-7).
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 variant
1, 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 BNT162b2
2. 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.
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More information
Accepted/In Press date: 1 March 2021
e-pub ahead of print date: 11 March 2021
Published date: 6 May 2021
Additional Information:
We thank the Cambridge University Hospitals NHS Trust Occupational Health Department; the NIHR Cambridge Clinical Research Facility and staff at CUH; E. Lim and G. Okecha; J. Voss for the gift of HeLa cells that stably express ACE2. R.K.G. is supported by a Wellcome Trust Senior Fellowship in Clinical Science (WT108082AIA). L.E.M. is supported by a Medical Research Council Career Development Award (MR/R008698/1). S.A.K. is supported by the Bill and Melinda Gates Foundation via PANGEA grant OPP1175094. D.A.C. is supported by a Wellcome Trust Clinical PhD Research Fellowship. K.G.C.S. is the recipient of a Wellcome Investigator Award (200871/Z/16/Z). This research was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, the Cambridge Clinical Trials Unit (CCTU) and the NIHR BioResource. This study was supported by the National Institute of General Medical Sciences (R01GM120553 to D.V.), the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C to D.V.), a Pew Biomedical Scholars Award (D.V.), an Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund (D.V.) and Fast Grants (D.V.). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. I.A.T.M.F. is funded by a SANTHE award (DEL-15-006).
Identifiers
Local EPrints ID: 453271
URI: http://eprints.soton.ac.uk/id/eprint/453271
ISSN: 1476-4687
PURE UUID: da857c70-6c56-4af8-82aa-1aec4ae006b3
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Date deposited: 11 Jan 2022 17:51
Last modified: 17 Mar 2024 03:56
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Contributors
Author:
Kordo Saeed
Author:
Siona Silveira
Author:
Eleri Wilson-Davies
Author:
Adhyana Mahanama
Author:
Buddhini Samaraweera
Author:
Sarah Jeremiah
Corporate Author: The COVID-19 Genomics UK (COG-UK) Consortium
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