Cited by 461SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesAnimal Virus Infections Studies

The DOI matches its Crossref record; 56 of the 60 references it cites were found in a registry or an index, and 2 are not checked yet; none of the 10 sources its claims cite is checked for support yet.

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

Open access

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.

Checked 2026-10-06 · 2 references not checked yet

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

The SARS-CoV-2 B.1.1.7 variant is harder to neutralize than the early Victoria strain by convalescent and vaccine sera, with reduced potency partly attributable to the N501Y spike mutation. However, the paper finds no widespread escape from monoclonal antibodies or from natural infection- or vaccine-induced antibody responses.

Key findings

  • B.1.1.7 required higher serum concentrations for neutralization: convalescent plasma FRNT50 titers were 2.9-fold lower against B.1.1.7 than Victoria (geometric mean, n = 34, p < 0.0001); AstraZeneca AZD1222 vaccine sera showed 2.5-fold (n = 15, p < 0.0001) and 2.1-fold (n = 10, p < 0.002) reductions at 14 and 28 days after the second dose; Pfizer-BioNTech BNT162b2 sera showed a 3.3-fold reduction (n = 25, p < 0.0001).
  • N501Y increased RBD binding affinity for ACE2 approximately 7-fold by biolayer interferometry: WT RBD(501N)-ACE2 KD 75.1 nM versus RBD(501Y)-ACE2 KD 10.7 nM, due to a slower off rate.
  • Some public IGHV3-53 antibodies were affected: mAbs 150, 158, and 175 showed roughly 3-fold reduced affinity, mAb 269 was hypersensitive with a 30-fold affinity effect and almost complete loss of neutralization, and mAb 278 failed to reach 100% neutralization with a maximum of 78%. Regeneron and AstraZeneca antibodies showed only modest or no reduction.
  • Plasma from 13 patients infected with B.1.1.7 showed no significant difference in neutralization titers between B.1.1.7 and Victoria strains.

Methods

  • The study analyzed 377 spike-targeting mAbs from first-wave SARS-CoV-2 cases, focusing on 20 potent neutralizing antibodies (19 anti-RBD, 1 anti-NTD), using BLI binding assays, crystallography of Fab 269 with WT and N501Y RBD, and focus reduction neutralization tests (FRNT) against Victoria and B.1.1.7.
  • Neutralization was tested with 34 convalescent plasma samples, AstraZeneca AZD1222 vaccine sera at 14 days (n = 15) and 28 days (n = 10) after the second dose, Pfizer-BioNTech BNT162b2 vaccine sera (n = 25) 7–17 days after the second dose, and plasma from 13 B.1.1.7-infected patients.
  • COG-UK sequence analysis examined 180,000 sequences; statistical comparisons used the Wilcoxon matched-pairs signed-rank test with two-tailed p values and geometric means.

Limitations

  • Stated: correlates of protection from SARS-CoV-2 are not established; in vitro neutralization assays do not capture contributions from T cells, Fcγ receptor interactions, or complement activation; convalescent plasma and vaccine serum were taken relatively soon after infection or vaccination, so titers may drop over time.
  • Stated: further work is needed to understand antibody responses to B.1.1.7, including adaptation to N501Y and NTD deletions, and to test neutralization of other variants such as B.1.351 and P.1.
  • Evident from the text: some groups were small (e.g., n = 10, n = 13, n = 15, n = 25), and the study reports in vitro neutralization only, without in vivo protection or durability data.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2021.02.033

Cites

56 of 58 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 10 cited sources checked · 0 supported · 0 flagged

Show all 29 claims

  • Probably not a substantial claim. 24
  • It may state two separate claims as one. 24
38 of 38
  • The authors state this as an assumption.

    A further increase in ACE2 affinity will increase the likelihood that stochastic virus attachment events lead to localization for sufficient time to trigger internalization.

    “It is reasonable to assume that a further increase in affinity will increase the likelihood of the stochastic events of virus attachment resulting in localization for sufficient time to trigger, perhaps by the recruitment of additional receptors, internalization of the virus.”
  • The paper relies on this without support.

    The higher affinity of SARS-CoV-2 for ACE2 underlies its greater transmission.

    “the higher affinity for ACE2 of SARS-CoV-2 has been imputed to underlie its greater transmission.”
  • The paper relies on this without support.

    The Pfizer vaccinees had no prior SARS-CoV-2 infection at entry.

    “participants were to the best of their knowledge seronegative at entry”
    “Vaccinees were Health Care Workers, based at Oxford University Hospitals NHS Foundation Trust, not known to have prior infection with SARS-C0V-2.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting cryoprotectant descriptions for the unmutated RBD/269 crystals

    Minor

    N501 RBD denotes the unmutated RBD. The methods say its crystals were dipped in a glycerol-containing solution, then say no cryoprotectant was used for RBD/269 crystals.

  • Sequence-download date precedes the analyzed isolates

    Minor

    The methods say the sequences were downloaded in January 2020, but the analysis includes isolates from December 2020. The stated download date cannot account for those isolates.

2 of 2

Citations

Cites

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2 of the 60 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Nelson, 2021, bioRxiv
  2. Zhu, 2021, Cryo-EM Structure of the N501Y SARS-CoV-2 Spike Protein in Complex with a Potent Neutralizing Antibody, bioRxiv

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Metadata

Authors
Supasa, P., Zhou, D., Dejnirattisai, W., Liu, C., Mentzer, A. J., Ginn, H. M., Zhao, Y., Duyvesteyn, H. M. E., Nutalai, R., Tuekprakhon, A., Wang, B., Paesen, G. C., Slon-Campos, J., López-Camacho, C., Hallis, B., Coombes, N., Bewley, K. R., Charlton, S., Walter, T. S., Barnes, E., Dunachie, S. J., Skelly, D., Lumley, S. F., Baker, N., Shaik, I., Humphries, H. E., Godwin, K., Gent, N., Sienkiewicz, A., Dold, C., Levin, R., Dong, T., Pollard, A. J., Knight, J. C., Klenerman, P., Crook, D., Lambe, T., Clutterbuck, E., Bibi, S., Flaxman, A., Bittaye, M., Belij-Rammerstorfer, S., Gilbert, S., Hall, D. R., Williams, M. A., Paterson, N. G., James, W., Carroll, M. W., Fry, E. E., Mongkolsapaya, J., Ren, J., Stuart, D. I., & Screaton, G. R.
Affiliations
  • Centre for Human Genetics (GB)
  • Diamond Light Source (GB)
  • Public Health England (GB)
  • University of Oxford (GB)
  • Worthing Hospital (GB)
  • Siriraj Hospital (TH)
Corresponding author
  • Mongkolsapaya, Juthathip
  • Ren, Jingshan
  • Stuart, David I.
  • Screaton, Gavin R.
Venue
Cell
Publisher
Elsevier BV
Published
2021-04
Volume
184
Issue
8
Pages
2201-2211.e7
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3129558828
Cited by
460
References
60
Citations by year
2025: 15 · 2024: 24 · 2023: 60 · 2022: 171 · 2021: 188
FWCI
35.16
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Greater South Information System
Funders
  • UK Research and Innovation
  • MRC (MR/N00065X/1)
  • China Academy of Chinese Medical Sciences (2018-I2M-2-002)
  • National Institute for Health Research (203141/Z/16/Z, 095541/A/11/Z, 090532/Z/09/Z)
  • Coalition for Epidemic Preparedness Innovations
  • Department of Health and Social Care
  • NIHR Oxford Biomedical Research Centre
  • National Institutes of Health (U19 I082360, WT204969/Z/16/Z)
  • Wellcome Trust (101122/Z/13/Z)
  • Cancer Research UK (C375/A17721)
  • Chinese Academy of Medical Sciences
  • Public Health England
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Keywords
SARS-CoV-2, B.1.1.7 variant, N501Y mutation, spike protein, antibody neutralization, antibody escape, monoclonal antibodies, convalescent sera, ACE2 binding
MeSH terms
COVID-19, SARS-CoV-2, Animals, Antibodies, Monoclonal, Antibodies, Viral, Chlorocebus aethiops, Cricetulus, Humans, Protein Binding, Structure-Activity Relationship, Vero Cells, CHO Cells, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Spike Glycoprotein, Coronavirus

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