SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies
Open accessPreprint — published as 10.1038/s41586-021-03412-7 · Paper page
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) transmission is uncontrolled in many parts of the world, compounded in some areas by higher transmission potential of the B1.1.7 variant now seen in 50 countries. It is unclear whether responses to SARS-CoV-2 vaccines based on the prototypic strain will be impacted by mutations found in B.1.1.7. Here we assessed immune responses following vaccination with mRNA-based vaccine BNT162b2. We measured neutralising antibody responses following a single immunization using pseudoviruses expressing the wild-type Spike protein or the 8 amino acid mutations found in the B.1.1.7 spike protein. The vaccine sera exhibited a broad range of neutralising titres against the wild-type pseudoviruses that were modestly reduced against B.1.1.7 variant. This reduction was also evident in sera from some convalescent patients. Decreased B.1.1.7 neutralisation was also observed with monoclonal antibodies targeting the N-terminal domain (9 out of 10), the Receptor Binding Motif (RBM) (5 out of 31), but not in neutralising mAbs binding outside the RBM. Introduction of the E484K mutation in a B.1.1.7 background to reflect newly emerging viruses in the UK led to a more substantial loss of neutralising activity by vaccine-elicited antibodies and mAbs (19 out of 31) over that conferred by the B.1.1.7 mutations alone. E484K emergence on a B.1.1.7 background represents a threat to the vaccine BNT162b.
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Neutralizing activity of vaccinee sera against B.1.1.7 is largely intact, and no adverse effects on current vaccines are expected.
“As for the ramifications of our findings for the protective efficacy of current SARS-CoV-2 vaccines, the neutralizing activity of sera from vaccinated individuals against B.1.1.7 is largely intact and no adverse effects on current vaccines are expected (Fig. 4c), consistent with conclusions that were reached by other studies 34,40,41 .”
From Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 (2021) · cites this paper as [40]
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Dopico, X. C., Ols, S., Loré, K., & Hedestam, G. B. K. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13372 · Cited by 164 · see citing works
Omicron spike function and neutralizing activity elicited by a comprehensive panel of vaccines
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Self-citationWillingness to Receive the Booster COVID-19 Vaccine Dose in Poland
Rzymski, P., Poniedziałek, B., & Fal, A. (2021) · Vaccines · doi:10.3390/vaccines9111286 · Cited by 160 · see citing works
Emerging SARS-CoV-2 Variants: A Review of Its Mutations, Its Implications and Vaccine Efficacy
Ramesh, S., Govindarajulu, M., Parise, R. S., Neel, L. T., Shankar, T., Patel, S., Lowery, P., Smith, F., Dhanasekaran, M., & Moore, T. (2021) · Vaccines · doi:10.3390/vaccines9101195 · Cited by 152 · see citing works
SARS-CoV-2 one year on: evidence for ongoing viral adaptation
Peacock, T. P., Penrice-Randal, R., Hiscox, J. A., & Barclay, W. (2021) · Journal of General Virology · doi:10.1099/jgv.0.001584 · Cited by 149 · see citing works
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Attwood, S. W., Hill, S. C., Aanensen, D. M., Connor, T. R., & Pybus, O. G. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00483-8 · Cited by 150 · see citing works
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de Palma, A., Vosough, S., & Liao, F. (2022) · Transportation Research Part A Policy and Practice · doi:10.1016/j.tra.2022.03.024 · Cited by 169 · see citing works
SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion
Ferreira, I. A. T. M., Kemp, S. A., Datir, R., Saito, A., Meng, B., Rakshit, P., Takaori-Kondo, A., Kosugi, Y., Uriu, K., Kimura, I., et al. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiab368 · Cited by 151 · see citing works
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The origins and molecular evolution of SARS-CoV-2 lineage B.1.1.7 in the UK
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Applications of Molecular Dynamics Simulation in Protein Study
Sinha, S., Tam, B., & Wang, S. M. (2022) · Membranes · doi:10.3390/membranes12090844 · Cited by 144 · see citing works
Evolutionary trajectory of SARS-CoV-2 and emerging variants
Singh, J., Pandit, P., McArthur, A. G., Banerjee, A., & Mossman, K. L. (2021) · Virology Journal · doi:10.1186/s12985-021-01633-w · Cited by 144 · see citing works
Bager, P., Wohlfahrt, J., Fonager, J., Rasmussen, M., Albertsen, M., Michaelsen, T., Møller, C. H., Ethelberg, S., Legarth, R., Button, M. S. F., et al. (2021) · Lancet. Infectious Diseases (Print) · doi:10.1016/s1473-3099(21)00290-5 · Cited by 114 · see citing works
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Kleanthous, H., Silverman, J., Makar, K., Yoon, I., Jackson, N. A. C., & Vaughn, D. (2021) · npj Vaccines · doi:10.1038/s41541-021-00393-6 · Cited by 137 · see citing works
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Becker, M., Dulovic, A., Junker, D., Ruétalo, N., Kaiser, P. D., Pinilla, Y. T., Heinzel, C., Häring, J., Traenkle, B., Wagner, T. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23473-6 · Cited by 135 · see citing works
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Li, Y., Liu, D., Wang, Y., Su, W., Liu, G., & Dong, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.638573 · Cited by 134 · see citing works
Fast-spreading COVID variant can elude immune responses
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SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development
Ao, D., Lan, T., He, X., Liu, J., Chen, L., Baptista‐Hon, D. T., Zhang, K., & Wei, X. (2022) · MedComm · doi:10.1002/mco2.126 · Cited by 117 · see citing works
- Authors
- Collier, D. A., De Marco, A., Ferreira, I. A. T. M., Meng, B., Datir, R., Walls, A. C., Kemp S, S. A., Bassi, J., Pinto, D., Fregni, C. S., Bianchi, S., Tortorici, M. A., Bowen, J., Culap, K., Jaconi, S., Cameroni, E., Snell, G., Pizzuto, M. S., Pellanda, A. F., Garzoni, C., Riva, A., The CITIID-NIHR BioResource COVID-19 Collaboration, Elmer, A., Kingston, N., Graves, B., McCoy, L. E., Smith, K. G., Bradley, J. R., Temperton, N., Ceron-Gutierrez L, L., Barcenas-Morales, G., The COVID-19 Genomics UK (COG-UK) consortium, Harvey, W., Virgin, H. W., Lanzavecchia, A., Piccoli, L., Doffinger, R., Wills, M., Veesler, D., Corti, D., & Gupta, R. K.
- Affiliations
- University of Cambridge (GB)
- University of Washington (US)
- Vir Biotechnology (Switzerland) (CH)
- VIR Biotechnology (United States) (US)
- Clinica Luganese Moncucco (CH)
- University of Milan (IT)
- Addenbrooke's Hospital (GB)
- University of Kent (GB)
- University of Glasgow (GB)
- Corresponding author
- Corti, Davide
- Gupta, Ravindra K.
- ORCID
- Collier, Dami A.
- Ferreira, Isabella A.T.M.
- Meng, Bo
- Datir, Rawlings
- Walls, Alexandra C.
- Bassi, Jessica
- Pinto, Dora
- Bianchi, Siro
- Tortorici, M. Alejandra
- Bowen, John
- Culap, Katja
- Jaconi, Stefano
- Cameroni, Elisabetta
- Snell, Gyorgy
- Pizzuto, Matteo S.
- Pellanda, Alessandra Franzetti
- Garzoni, Christian
- Riva, Agostino
- McCoy, Laura E
- Smith, Kenneth GC
- Bradley, John R.
- Temperton, Nigel
- Harvey, William
- Virgin, Herbert W.
- Lanzavecchia, Antonio
- Piccoli, Luca
- Wills, Mark
- Veesler, David
- Corti, Davide
- Gupta, Ravindra K.
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-01-20
- Volume
- 593
- Issue
- 7857
- Pages
- 136-141
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC7899479
- OpenAlex
- W3134446480
- Cited by
- 729
- References
- 65
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 40 · 2023: 61 · 2022: 254 · 2021: 346 · 2020: 4
- FWCI
- 55.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Northumbria Research Link (Northumbria University) (acceptedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- PubMed Central (acceptedVersion, cc-by)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- Burroughs Wellcome Fund
- Bill and Melinda Gates Foundation (OPP 1175094)
- University of Portsmouth
- Fordham University
- Northumbria University
- Wellcome Trust (R01GM120553, 200871, 108082/A/15/Z, 200871/Z/16/Z, 108082, 204911/Z/16/Z, HHSN272201700059C, WT108082AIA, DEL-15-006, DP1AI158186)
- University Hospital Southampton NHS Foundation Trust
- King's College Hospital NHS Foundation Trust
- Public Health Wales
- Fast Grants
- Vir Biotechnology
- Cancer Research UK (23923)
- National Institute for Health and Care Research (NF-SI-0514-10109, NIHR301445, OPP1175094, ACF-2018-04-014)
- Department of Health and Social Care (HHSN272201700059C)
- Academy of Medical Sciences (AMS-CSF4-Torok, SBF004/1052)
- University of Cambridge
- University of East Anglia
- University of Exeter
- University of Southampton
- University of Warwick
- King's College London
- University College London
- University of Oxford
- University of Birmingham
- Queen's University Belfast
- Swansea University
- Public Health Agency
- Public Health England
- Cambridge University Hospitals (BRC 2017-22)
- Queen's University
- Oxford University Hospitals NHS Foundation Trust
- Quadram Institute Bioscience
- University Hospitals Coventry and Warwickshire NHS Trust
- National Institutes of Health (1s10od023476-01)
- Directorate for Biological Sciences
- NIHR BioResource
- Medical Research Council (MR/P008801/1, 200871/Z/16/Z, MR/R008698/1, MR/S00081X/1, MC_UP_1201/16)
- Warwick Medical School
- NIHR Cambridge Biomedical Research Centre
- National Institute of General Medical Sciences (R01GM120553)
- National Institute of Allergy and Infectious Diseases (HHSN272201700059C, DP1AI158186)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, B.1.1.7 variant, Omicron variant, BNT162b2, mRNA vaccines, neutralizing antibodies, vaccine escape, spike protein mutations, monoclonal antibodies, receptor-binding motif, N-terminal domain, COVID-19 vaccine efficacy
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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