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Cross-neutralisation of variants in convalescent plasma — small SA study

Antibodies from individuals in South Africa who had recovered from a SARS-CoV-2 infection from the first wave of the epidemic are less effective at neutralising the new variant of concern (501Y.V2) circulating in South Africa, a study reports.

Conversely, the authors at the Africa Health Research Institute, Durban, University of KwaZulu-Natal, KwaZulu-Natal Research Innovation and Sequencing Platform, The Institute for Medical Research Israel-Canada, Hadassah Medical School, The Hebrew University of Jerusalem, University College London, Centre for the AIDS Programme of Research in South Africa, Ragon Institute of MGH/Harvard, and MIT, Nelson R Mandela School of Clinical Medicine, University of Washington in Seattle and the Max Planck Institute for Infection Biology – Berlin, show that plasma from six patients who were infected with the 501Y.V2 variant of SARS-CoV-2 during the second wave of the epidemic in South Africa is effective at neutralising the strain that circulated during the first wave.

The findings suggest that vaccines based on SARS-CoV-2 variants of concern may provide effective activity against other circulating strains.

New SARS-CoV-2 variants of concern have emerged with mutations that give the virus an advantage over other strains. Recent results from vaccine trials from Novavax, Johnson and Johnson and AstraZeneca in South Africa indicate that circulation of the 501Y.V2 variant, which has become dominant in parts of South Africa, may lead to a decrease in vaccine effectiveness. Understanding how antibodies against one variant might act against another could inform vaccine development.

Alex Sigal and colleagues compare the neutralising activity of convalescent plasma from individuals with COVID-19 on SARS-CoV-2 variants from the first and the current (second) wave of the epidemic in South Africa. They took plasma and sequenced the infecting virus from 14 individuals who had COVID-19 during the first wave; of these participants, only one was recorded to have a notable SARS-CoV-2 mutation (which encodes a substitution called E484K), but none of the participants was infected with a virus containing the mutations associated with 501Y.V2.

They did the same with six individuals who were infected during the second wave; in this case, all of the participants were infected with the 501Y.V2 variant.

Plasma from patients from the first wave (excluding the individual with the E484K variant) was less effective at neutralising the 501Y.V2 variant in laboratory tests compared with the neutralisation of the first-wave SARS-CoV-2 virus.

However, plasma from the patients from the second wave effectively neutralised the virus from the first wave. Plasma elicited by the variant with the E484K substitution alone showed much stronger neutralisation of both the first-wave and 501Y.V2 virus variants, but as this substitution was observed in only one participant, the result is difficult to interpret, the authors note.

The authors conclude that a vaccine that is designed to target 501Y.V2 may also be effective against other SARS-CoV-2 variants.


Study details
Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

Sandile Cele, Inbal Gazy, Laurelle Jackson, Shi-Hsia Hwa, Houriiyah Tegally, Gila Lustig, Jennifer Giandhari, Sureshnee Pillay, Eduan Wilkinson, Yeshnee Naidoo, Farina Karim, Yashica Ganga, Khadija Khan, Mallory Bernstein, Alejandro B. Balazs, Bernadett I Gosnell, Willem Hanekom, Mahomed-Yunus S. Moosa, NGS-SA, COMMIT-KZN Team, Richard J Lessells, Tulio de Oliveira, Alex Sigal

Published in Nature on 29 March 2021

SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations and may reduce the efficacy of current vaccines targeting the spike glycoprotein. Here, using a live virus neutralization assay (LVNA), we compared neutralization of a non-VOC variant 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 mutations, except for one with the E484K mutation in the receptor binding domain. 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 a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma across participants. In contrast, second wave plasma cross-neutralization of first wave virus was more effective, showing only a 2.3-fold decline relative to first wave plasma neutralization of first wave virus. 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.


Nature study (Restricted access)



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South Africa variant elicits cross-reactive neutralising antibodies

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