Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
Open accessAbstract
The COVID-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Single and combination monoclonal antibody (mAb) therapeutics have received emergency use authorization 1–3 , with more in the pipeline 4–7 . Furthermore, multiple vaccine constructs have shown promise 8 , including two with ~95% protective efficacy against COVID-19 9,10 . However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. The recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK 11 and B.1.351 in South Africa 12 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a few mAbs to the receptor-binding domain (RBD). It is not more resistant to convalescent plasma or vaccinee sera. Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants 13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Mutations found in emergent S variants decrease sensitivity to neutralization by mAbs, convalescent plasma, and sera from vaccinated individuals.
“Mutations found in emergent S variants decrease sensitivity to neutralization by mAbs, convalescent plasma, and sera from vaccinated individuals (27, 37, 58, 61–70).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [66]
Reduced sensitivity to vaccine-elicited nAbs has been reported for other B.1.351 variants.
“Reduced sensitivity to vaccine-elicited nAbs has been reported for other B.1.351 variants (66, 83, 84).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [66]
Further mutations in spike protein observed in other novel lineages appear to be driven by escape of the virus from the neutralising activity of public antibodies, indicating that prevention of transmission might be temporary as the virus adapts to natural or vaccine-induced immunity.
“However, it should be noted that further mutations in spike protein observed in other novel lineages7, 8 appear to be driven by escape of the virus from the neutralising activity of public antibodies,40, 41 indicating that prevention of transmission might be temporary as the virus adapts to natural or vaccine-induced immunity.”
Post-vaccination sera derived from volunteers receiving either of the mRNA vaccines showed 6.5- to 8.6-fold reductions in neutralizing capacity to the B.1.351 variant relative to prototype virus in pseudovirus neutralization.
“post-vaccination sera derived from volunteers receiving either of the mRNA vaccines showed 6.5- to 8.6-fold reductions in neutralizing capacity to the B.1.351 variant relative to prototype virus in pseudovirus neutralization17”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [17]
The E484K mutation has been reported to abolish or substantially reduce neutralization by multiple potent monoclonal antibodies and polyclonal convalescent sera in both wild-type and pseudo-virus neutralization assays.
“The E484K mutation has been reported to abolish or substantially reduce neutralization by multiple potent monoclonal antibodies and polyclonal convalescent sera in both wild-type and pseudo-virus neutralization assays.12,13,17,18,22”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [17]
The B.1.351 variant is characterized by three deleterious mutations at key antigenic sites in the RBD, including N501Y, K417N, and E484K.
“The B.1.351 variant is characterized by three deleterious mutations at key antigenic sites in the RBD, including N501Y, K417N, and E484K, with the latter two having particular functional impact.”
From Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant (2021) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cited by
Sorted by citations
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma
Wibmer, C. K., Ayres, F., Hermanus, T., Madzivhandila, M., Kgagudi, P., Oosthuysen, B., Lambson, B. E., de Oliveira, T., Vermeulen, M., van der Berg, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01285-x · Cited by 1,147 · see citing works
Chen, R. E., Zhang, X., Case, J. B., Winkler, E. S., Liu, Y., VanBlargan, L. A., Liu, J., Errico, J. M., Xie, X., Suryadevara, N., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01294-w · Cited by 881 · see citing works
Emary, K. R. W., Golubchik, T., Aley, P. K., Ariani, C. V., Angus, B., Bibi, S., Blane, B., Bonsall, D., Cicconi, P., Charlton, S., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00628-0 · Cited by 603 · see citing works
mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection
Stamatatos, L., Czartoski, J., Wan, Y.-H., Homad, L. J., Rubin, V., Glantz, H., Neradilek, M., Seydoux, E., Jennewein, M. F., MacCamy, A. J., et al. (2021) · Science · doi:10.1126/science.abg9175 · Cited by 557 · see citing works
Preliminary Efficacy of the NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant
Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., Lalloo, U., Masilela, M. S. L., Moodley, D., Hanley, S., et al. (2021) · doi:10.1101/2021.02.25.21252477 · Cited by 625 · see citing works
Efficacy of NVX-CoV2373 Covid-19 Vaccine against the B.1.351 Variant
Shinde, V., Bhikha, S., Hoosain, Z., Archary, M., Bhorat, Q., Fairlie, L., Lalloo, U., Masilela, M. S. L., Moodley, D., Hanley, S., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2103055 · Cited by 625 · see citing works
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies
Greaney, A. J., Starr, T. N., Barnes, C. O., Weisblum, Y., Schmidt, F., Caskey, M., Gaebler, C., Cho, A., Agudelo, M., Finkin, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24435-8 · Cited by 433 · see citing works
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
Yuan, M., Huang, D., Lee, C.-C. D., Wu, N. C., Jackson, A. M., Zhu, X., Liu, H., Peng, L., van Gils, M. J., Sanders, R. W., et al. (2021) · doi:10.1101/2021.02.16.430500 · Cited by 364 · see citing works
Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail
Dong, J., Zost, S. J., Greaney, A. J., Starr, T. N., Dingens, A. S., Chen, E. C., Chen, R. E., Case, J. B., Sutton, R. E., Gilchuk, P., et al. (2021) · doi:10.1101/2021.01.27.428529 · Cited by 55 · see citing works
Zhou, H., Dcosta, B. M., Samanovic, M. I., Mulligan, M. J., Landau, N. R., & Tada, T. (2021) · mBio · doi:10.1128/mbio.01386-21 · Cited by 68 · see citing works
Faulkner, N., Ng, K. W., Wu, M. Y., Harvey, R., Margaritis, M., Paraskevopoulou, S., Houlihan, C., Hussain, S., Greco, M., Bolland, W., et al. (2021) · eLife · doi:10.7554/elife.69317 · Cited by 52 · see citing works
Martin, D. P., Weaver, S., Tegally, H., San, E. J., Shank, S. D., Wilkinson, E., Lucaci, A. G., Giandhari, J., Naidoo, S., Pillay, Y., et al. (2021) · doi:10.1101/2021.02.23.21252268 · Cited by 291 · see citing works
Tada, T., Dcosta, B. M., Samanovic-Golden, M., Herati, R. S., Cornelius, A., Mulligan, M. J., & Landau, N. R. (2021) · doi:10.1101/2021.02.05.430003 · Cited by 153 · see citing works
Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
Cele, S., Gazy, I., Jackson, L., Hwa, S.-H., Tegally, H., Lustig, G., Giandhari, J., Pillay, S., Wilkinson, E., Naidoo, Y., et al. (2021) · doi:10.1101/2021.01.26.21250224 · Cited by 651 · see citing works
- Authors
- Wang, P., Nair, M. S., Liu, L., Iketani, S., Luo, Y., Guo, Y., Wang, M., Yu, J., Zhang, B., Kwong, P. D., Graham, B. S., Mascola, J. R., Chang, J. Y., Yin, M. T., Sobieszczyk, M., Kyratsous, C. A., Shapiro, L., Sheng, Z., Huang, Y., & Ho, D. D.
- Affiliations
- Aaron Diamond AIDS Research Center (US)
- National Institutes of Health (US)
- Regeneron (United States) (US)
- Corresponding author
- Huang, Yaoxing
- Ho, David D.
- ORCID
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-01-26
- Volume
- 593
- Issue
- 7857
- Pages
- 130-135
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC7852232
- OpenAlex
- W3123551159
- Cited by
- 2,328
- References
- 0
- Citations by year
- 2026: 34 · 2025: 101 · 2024: 136 · 2023: 301 · 2022: 757 · 2021: 990 · 2020: 7
- FWCI
- 172.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Bill and Melinda Gates Foundation
- JPB Foundation
- 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, SARS-CoV-2 variants, Beta variant, Alpha variant, antibody resistance, neutralizing antibodies, monoclonal antibodies, spike protein mutations, N-terminal domain, receptor binding domain, convalescent plasma, vaccine efficacy
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
