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Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
Open accessPreprint — published as 10.1038/s41586-021-03471-w · Paper page
Abstract
SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations and may reduce efficacy of current vaccines targeted at the spike glycoprotein. We re-cently described the emergence of VOC in South Africa (501Y.V2 or PANGO lineage B.1.351) with mutations in the spike receptor-binding domain (RBD) and N-terminal domain (NTD). Here, using a live virus neutralization assay (LVNA), we compared neutralization of a first wave virus (B.1.1.117) versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections. Sequencing demonstrated that infections in first wave plasma donors were with viruses harbouring none of the 501Y.V2-defining RBD or NTD mutations, except for one with E484K. 501Y.V2 virus was effectively neutralized by plasma from second wave infections and first wave virus was effectively neutralized by first wave plasma. In cross-neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with an 8.4-fold drop in neutralization relative to first wave virus and a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma. In contrast, second wave plasma neutralization of first wave virus was more effective, showing 4.1-fold decline relative to 501Y.V2 virus neutralization and 2.3-fold decline relative to first wave plasma neutralization. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants. The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages.
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“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 [12]
In the citing paper
“A recent report using infectious B.1.351virus showed that plasma samples from six convalescent donors were strongly attenuated against this strain, with half-maximal inhibitory concentration (IC 50 ) values 6-to 200-fold higher than ancestral virus 29 .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [29]
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Metadata
- Authors
- Cele, S., 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., NGS-SA, COMMIT-KZN Team, Lessells, R. J., Oliveira, T. D., & 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.
- Oliveira, Tulio de
- Sigal, Alex
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-01-26
- Volume
- 593
- Issue
- 7857
- Pages
- 142-146
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC9867906
- OpenAlex
- W3148277587
- Cited by
- 651
- References
- 29
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 28 · 2023: 63 · 2022: 199 · 2021: 320
- FWCI
- 48.30
- 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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