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A paper published yesterday by Public Health England (PHE) on the investigation of the novel SARS-CoV-2 variant, B.1.1.7, mentions on page 17 the detection of E484K mutation in some B.1.1.7 genomes.
Dr Jonathan Stoye, Group Leader, Retrovirus-Host Interactions Laboratory, The Francis Crick Institute, said:
“The Brazilian and South African variants of SARS-CoV-2 are defined by characteristic constellations of around 10 differences in the 1273 amino acid long Spike protein. One mutation shared between the two variants is the E484K change which causes some loss of sensitivity to immune responses that give protection against virus infection. The E484K mutation now been identified in a small fraction of viruses carrying sequence differences defining the UK variant. This suggests that the UK variant is now independently acquiring the E484K change. From a virological standpoint, appearance of new variants by mutation during replication cannot be considered surprising. Whether this change will provide significant growth advantages for the novel virus causing it to predominate remains to be seen. This report would seem to suggest that under conditions of very high levels of virus replication even the most stringent of border controls, although they may delay spread, are unlikely to prevent the appearance of new variants.”
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:
“This updated PHE report on the UK B.1.1.7/VOC 202012/01 mentions the acquisition of the E484K mutation – which is a worrying development, though not entirely unexpected.
“This E484K mutation is already present in the South African B.1.351/501Y.V2 and Brazilian B.1.1.28/P1/P2 variants – and is now thought to be the main mutation impacting on vaccine efficacy.
“The acquisition may be due to recombination with one of the South African/Brazilian variant viruses that may have co-infected the same cell – as we see with different influenza viruses – but this is rarer with coronaviruses.
“So this may be more likely to have arisen through convergent/parallel natural selection/evolution within the human population as the virus adapts to this new host – viruses can only evolved through continuous replication.
“This is another reason to follow the COVID-19 restrictions/infection control measures more strictly – otherwise not only can the virus continue to spread, it can also evolve.
“Unfortunately, the lack of control of these different variants in the UK may lead this population to become a melting pot for different emerging SARS-COV-2/COVID-19 variants – so we really need to reduce our contact rates to reduce the opportunities for viral spread/replication to reduce the speed with which these different virus variants can evolve.
“Closing borders/restricting travel may help a little with this, but there is now probably already a sufficient critical mass of virus-infected people within the endemic UK population to allow this natural selection/evolution to proceed – as this report suggests – so we really need to stick to the COVID-19 lockdown restrictions as much as possible.
“If this E484K mutation is acquired by most of the UK B.1.1.7 variants – the recent reassurances from recent studies showing that the mRNA vaccines will still offer optimum protection against the original UK variant – may no longer apply.”
Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:
“The detection of the E484K mutation in the ‘Kent’ variant of the Covid-19 coronavirus is of concern, but ultimately no surprise. It is the mutation causing the most concern in the ‘South African’ and ‘Brazilian’ variants. While to date only one case has been identified, it seems highly likely that there will be more in the coming weeks and months. It does not mean that this mutation is present in all versions of this variant.
“Mutations arise spontaneously and thrive if they provide the virus with an advantage. In lab studies, this mutation meant that antibodies were less able to bind to the virus’ spike protein in order to stop it from unlocking human cells to gain entry. Clinical trials by Novavax and Johnson & Johnson showed that their new vaccines were less effective in South Africa, compared to the UK or USA, and it is presumed that it was because of the high level of virus carrying this E484K mutation. While no assessments have yet been made on the effectiveness of the vaccines currently in use in this country, it is entirely possible that their efficacy will be similarly diminished by this mutation.”
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, University of Warwick, said:
“This E484K mutation, which has also been found in a Brazilian variant, appears to provide some escape from immune recognition – it prevents virus infection from being blocked by certain therapeutic monoclonal antibodies and reduces the efficiency of neutralising antibodies from convalescent sera from previously infected individuals.
“This change isn’t present in all B.1.1.7 variants but has arisen in a few cases probably as a consequence of immune selection.
“An acquisition event means that the E484K mutation has been acquired by the B.1.1.7 variant during the process of virus replication and selection for virus variants that are more able to grow in the presence of an antibody response. This is a concern. It shows that the virus is very likely to be adapting to our immune response.
“Early results from the Novavax and Janssen vaccine trials show reductions in the ability of the vaccines to protect from disease in South Africa as compared to vaccine responses in the UK or USA. The E484K mutation may be contributing to this reduction in vaccine efficacy. Novavax report a 60% efficacy of their vaccine in South Africa which is still a good response noting that the annual flu jab is also around 60% effective.
“There is also concern that the South African variant might be able to more efficiently re-infect individuals who have previously been infected with the original form of the virus. This is likely to be due, in part, to the E484K mutation which may weaken the immune response and also impact the longevity of the neutralising antibody response. So B.1.1.7 variants carrying the E484K mutation may be more efficient at re-infection.
“Whatever changes have occurred in the B.1.1.7 or any other virus variants, standard measures to restrict transmission (hands, face, space) will prevent infection.”
Declared interests
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