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Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
Open accessPublished version of a preprint
Abstract
SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations 1,2 and may reduce the efficacy of current vaccines that target the spike glycoprotein of SARS-CoV-2 3. Here, using a live-virus neutralization assay, we compared the neutralization of a non-VOC variant with the 501Y.V2 VOC (also known as B.1.351) using plasma collected from adults who were hospitalized with COVID-19 during the two waves of infection in South Africa, the second wave of which was dominated by infections with the 501Y.V2 variant. Sequencing demonstrated that infections of plasma donors from the first wave were with viruses that did not contain the mutations associated with 501Y.V2, except for one infection that contained the E484K substitution in the receptor-binding domain. The 501Y.V2 virus variant was effectively neutralized by plasma from individuals who were infected during the second wave. The first-wave virus variant was effectively neutralized by plasma from first-wave infections. However, the 501Y.V2 variant was poorly cross-neutralized by plasma from individuals with first-wave infections; the efficacy was reduced by 15.1-fold relative to neutralization of 501Y.V2 by plasma from individuals infected in the second wave. By contrast, cross-neutralization of first-wave virus variants using plasma from individuals with second-wave infections was more effective, showing only a 2.3-fold decrease relative to neutralization of first-wave virus variants by plasma from individuals infected in the first wave. Although we tested only one plasma sample from an individual infected with a SARS-CoV-2 variant with only the E484K substitution, this plasma sample potently neutralized both variants. The observed effective neutralization of first-wave virus by plasma from individuals infected with 501Y.V2 provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages.
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“In contrast, mutations in B.1.351 and P.1 variants are associated with the more pronounced loss of neutralizing capacity.15,16,22,23,25”
From Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals (2021) · cites this paper as [25]
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“In addition, Beta and Delta are relatively poorly neutralized by convalescent sera obtained from unvaccinated individuals infected with non-VOC virus ( 7 – 9 , 21 ).”
From Increased risk of SARS-CoV-2 reinfection associated with emergence of Omicron in South Africa (2021) · cites this paper as [7]
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RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study
Walsh, E. E., Frenck, R., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Mulligan, M. J., Bailey, R., et al. (2020) · doi:10.1101/2020.08.17.20176651 · Cited by 2,615
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Self-citationDetection of a SARS-CoV-2 variant of concern in South Africa
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Convergent Antibody Responses to SARS-CoV-2 in Convalescent Individuals
Robbiani, D. F., Gaebler, C., Muecksch, F., Lorenzi, J. C. C., Wang, Z., Cho, A., Agudelo, M., Barnes, C. O., Gazumyan, A., Finkin, S., et al. (2020) · Nature · doi:10.1038/s41586-020-2456-9 · Cited by 1,853
Self-citationEvolution of antibody immunity to SARS-CoV-2
Gaebler, C., Wang, Z., Lorenzi, J. C. C., Muecksch, F., Finkin, S., Tokuyama, M., Cho, A., Jankovic, M., Schaefer-Babajew, D., Oliveira, T. Y., et al. (2021) · Nature · doi:10.1038/s41586-021-03207-w · Cited by 1,674
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Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
Faria, N. R., Mellan, T. A., Whittaker, C., Claro, I. M., Candido, D. D. S., Mishra, S., Crispim, M. A. E., Sales, F. C. S., Hawryluk, I., McCrone, J. T., et al. (2021) · Science · doi:10.1126/science.abh2644 · Cited by 1,461
Piccoli, L., Park, Y.-J., Tortorici, M. A., Czudnochowski, N., Walls, A. C., Beltramello, M., Silacci-Fregni, C., Pinto, D., Rosen, L. E., Bowen, J. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.037 · Cited by 1,395
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
Garcia-Beltran, W. F., Lam, E. C., St. Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., Feldman, J., Pavlovic, M. N., Gregory, D. J., Poznansky, M. C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.013 · Cited by 1,353
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Detection of a SARS-CoV-2 variant of concern in South Africa
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03402-9 · Cited by 2,510
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Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
Faria, N. R., Mellan, T. A., Whittaker, C., Claro, I. M., Candido, D. D. S., Mishra, S., Crispim, M. A. E., Sales, F. C. S., Hawryluk, I., McCrone, J. T., et al. (2021) · Science · doi:10.1126/science.abh2644 · Cited by 1,461
Metadata
- Authors
- Network for Genomic Surveillance in South Africa, Cele, S., COMMIT-KZN Team, Gazy, I., Jackson, L., Hwa, S.-H., Tegally, H., Lustig, G., Giandhari, J., Pillay, S., Wilkinson, E., Naidoo, Y., Karim, F., Ganga, Y., Khan, K., Bernstein, M., Balazs, A. B., Gosnell, B. I., Hanekom, W., Moosa, M.-Y. S., Lessells, R. J., de Oliveira, T., & Sigal, A.
- Affiliations
- Africa Health Research Institute (ZA)
- Hebrew University of Jerusalem (IL)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- University of KwaZulu-Natal (ZA)
- Ragon Institute of MGH, MIT and Harvard (US)
- Max Planck Institute for Infection Biology (DE)
- Corresponding author
- Sigal, Alex
- ORCID
- Cele, Sandile
- Gazy, Inbal
- Jackson, Laurelle
- Hwa, Shi-Hsia
- Tegally, Houriiyah
- Lustig, Gila
- Giandhari, Jennifer
- Pillay, Sureshnee
- Wilkinson, Eduan
- Naidoo, Yeshnee
- Karim, Farina
- Ganga, Yashica
- Khan, Khadija
- Bernstein, Mallory
- Balazs, Alejandro B.
- Gosnell, Bernadett I.
- Hanekom, Willem
- Moosa, Mahomed-Yunus S.
- Lessells, Richard J.
- de Oliveira, Tulio
- Sigal, Alex
- Venue
- Nature
- Published
- 2021-03-29
- Volume
- 593
- Issue
- 7857
- Pages
- 142-146
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9867906
- OpenAlex
- W3148277587
- Cited by
- 651
- References
- 31
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 28 · 2023: 63 · 2022: 199 · 2021: 320
- FWCI
- 48.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Griffith Research Online (submittedVersion, other-oa)
- Funders
- South African Medical Research Council
- Inyuvesi Yakwazulu-Natali
- National Health Laboratory Service
- Medical Research Council
- National Institute on Drug Abuse (DP2DA040254)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2, Beta variant, convalescent plasma, neutralizing antibodies, cross-neutralization, vaccine efficacy, spike protein, receptor binding domain, COVID-19 pandemic, South Africa
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Serotherapy, Animals, Antibodies, Viral, Cell Line, Chlorocebus aethiops, Humans, Immunization, Passive, Mutation, Neutralization Tests, South Africa, Time Factors, Vero Cells, Immune Evasion, Antibodies, Neutralizing
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