Dominant SA variant escapes antibodies — AHRI and UKZN study

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The dominant new variant of the COVID-19 virus in South Africa, 501Y.V2, can escape antibodies generated from previous infection. This means that antibodies from people who were infected with previous variants may not work well against 501Y.V2. The research is led by Dr Alex Sigal, from the Africa Health Research Institute (AHRI) and Professor Tulio de Oliveira and Dr Richard Lessels, from the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) at the University of KwaZulu-Natal (UKZN).

Up until now it was not understood if the mutations in 501Y.V2 affected the ability of pre-existing antibodies to SARS-CoV-2 (the virus that causes COVID-19) to recognise and inhibit live 501Y.V2 variant. Using live virus outgrown from COVID-19 patients, the research team tested blood plasma, which contained antibodies from people who had recovered from COVID-19, against the new variant. They compared how much plasma was needed to neutralise, or make ineffective, the 501Y.V2 variant. They discovered that the antibodies of patients infected in the first wave in South Africa are much less able to neutralize 501Y.V2 relative to previous lineages of COVID-19 in South Africa.

“Compared to first-wave variants, we needed about a 6 to 200-fold higher plasma concentration to neutralise 501Y.V2 in a lab setting. This suggests that the mutations in the new variant may have caused the virus to lose a great deal of sensitivity to previous antibody immunity,” said AHRI faculty member and senior author of the paper, Sigal. “The ability of the virus to evolve may have been underestimated.”

“This work gives us important new insight into the key mutations that are found in the 501Y.V2,” said KRISP director and co-senior author de Oliveira. “These results with the live virus add to the growing body of evidence that the 484K mutation is a key mutation that allows the virus to escape neutralisation. It is the first time, to the best of my knowledge, that this is shown in a live 501Y.V2 virus.”

While the authors say the data is a cause for concern, they have also emphasised that more work needs to be done before they can say what this means for people’s immunity against 501Y.V2, as well as the implications for vaccines designed for the earlier variants. “The body’s immune response to viruses is complex and has many different facets – of which the antibody response is only one component. Vaccines may also give rise to a broader range of antibodies. This means that the other arms of the body’s immune system could still provide protection against 501Y.V2,” they said. Vaccination is still absolutely recommended and is the only long-term solution to this infection.

Following the identification of the rapidly spreading new variant in South Africa in late 2020, a group of leading South African scientists formed a consortium to conduct coordinated research into 501Y.V2 with the support of the South African Medical Research Council (SAMRC) and the Department of Science and Innovation (DSI). Their work includes investigating whether COVID-19 vaccines will work against the new variant.

“Currently, most vaccinologists believe that the vaccines will still work against the new variant. While the antibodies may be less effective, it is likely vaccines may produce a broader antibody response which will be harder to evade. Other parts of the immune response induced by vaccines, such as the T cell response, could also compensate,” said AHRI director and consortium co-lead, Professor Willem Hanekom. “In the context of this new variant, it is even more critical to get vaccines rolled-out urgently in South Africa.”

“The alarming emergence of COVID variants shows the vital role of genomic surveillance in the world,” added de Oliveira, who led the identification of the 501Y.V2 variant.

“Expanding our genomics surveillance network to include basic science, immunology and vaccinology in South Africa will allow us to quickly answer some of the most important questions related to the 501Y.V2 and other variants that may emerge in Africa.”

 

Study details
Escape of SARS-CoV-2 501Y.V2 variants 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, 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 medRxiv on 26 January 2021

Abstract
New SARS-CoV-2 variants with mutations in the spike glycoprotein have arisen independently at multiple locations and may have functional significance. The combination of mutations in the 501Y.V2 variant first detected in South Africa include the N501Y, K417N, and E484K mutations in the receptor binding domain (RBD) as well as mutations in the N-terminal domain (NTD). Here we address whether the 501Y.V2 variant could escape the neutralizing antibody response elicited by natural infection with earlier variants. We were the first to outgrow two variants of 501Y.V2 from South Africa, designated 501Y.V2.HV001 and 501Y.V2.HVdF002. We examined the neutralizing effect of convalescent plasma collected from six adults hospitalized with COVID-19 using a microneutralization assay with live (authentic) virus. Whole genome sequencing of the infecting virus of the plasma donors confirmed the absence of the spike mutations which characterize 501Y.V2. We infected with 501Y.V2.HV001 and 501Y.V2.HVdF002 and compared plasma neutralization to first wave virus which contained the D614G mutation but no RBD or NTD mutations. We observed that neutralization of the 501Y.V2 variants was strongly attenuated, with IC50 6 to 200-fold higher relative to first wave virus. The degree of attenuation varied between participants and included a knockout of neutralization activity. This observation indicates that 501Y.V2 may escape the neutralizing antibody response elicited by prior natural infection. It raises a concern of potential reduced protection against re-infection and by vaccines designed to target the spike protein of earlier SARS-CoV-2 variants.

 

Previous work by a team at the National Institute for Communicable Disease led by Penny Moore found 501Y.V2 could completely evade the antibodies generated in response to infection in South Africa’s first coronavirus wave in almost half the samples they studied. They also found 90% of these samples contained antibodies that were less effective at neutralising 501Y.V2.

The Times reports that her team has also investigated how antibodies generated in response to 501Y.V2 shape up against P1, the variant first detected in Brazil, and found they had some neutralising effect against this strain.

More work was now needed to determine why 501Y.V2 generated antibodies that offered a greater breadth of protection than other variants, said Moore. “That will be crucial to understanding the risk of reinfection and vaccine design,” she said.

Moore cautioned that scientists still did not know how long antibody protection lasted. “We strongly encourage people who have been infected to still pursue the same non-pharmaceutical interventions. You should not assume your antibodies are good enough to keep you safe from infection again,” she is quoted in The Times as saying.

 

Africa Health Research Institute material[/link]

 

medRxiv study (Restricted access)

 

Full report in The Times (Open access)

 

 

See also MedicalBrief archives:

Donor plasma not successful in treating South Africa variant — SA NICD study

 

Sixteen new SARS-CoV-2 lineages spread through South Africa from March to August 2020

 

‘Most South Africans have had COVID-19′ — National Blood Service study

 

KRISP director: It’s ‘unjust and damaging’ to call 501Y.V2 the ‘SA variant’

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