The E484K mutation - vaccine complications

The E484K mutation – a ‘backdoor’ to undoing vaccine efforts: As we are seeing many novel Covid-19 variants around the world, Professor Martin Michaelis and Dr Mark Wass of University of Kent’s School of Biosciences explain why this may be happening and what these new variants may mean:

‘After almost a year, in which SARS-CoV-2, the coronavirus that causes COVID-19, has not seemed to change its properties, troubling new variants of the virus seem to have only emerged in the last few weeks.

‘Although viruses like SARS-CoV-2 have high mutation rates, they may not change their features until there is a substantial selection pressure that favours new variants. One such selection pressure is caused by an increasing level of immunity in a population. Hence, it is no surprise that novel variants are found in places with high levels of COVID-19 spread or COVID-19 vaccination programmes, such as the UK, Brazil and South Africa.

‘Many of the new variants have mutations in the Spike (S) protein, the SARS-CoV-2 surface protein that mediates virus entry into host cells. The Spike protein is a main target of our defensive antibodies generated against infection. Current vaccines use different approaches to present the Spike protein to the immune system, so vaccine-mediated immunity is exclusively targeted towards the Spike protein, which is likely why we are now seeing these mutations.

‘Thus, it is probable that the novel variants are due to the selection pressure associated with increased levels of immunity provided by previous COVID-19 infections and vaccines. Many of the new variants harbour E484K mutation in the Spike protein, a mutation that is anticipated to reduce the protection gained from vaccination or previous infections.

‘The South African B.1.135 variant carries the E484K mutation, and the Novavax vaccine was much less effective in South Africa than in the UK. In Manaus in Brazil, there is a new surge in COVID-19 cases, although more than three quarters of the population have already been infected. P.1, a new variant also harbouring E484K, may be partly responsible.

‘P.1 and P.2, another novel Brazilian E484K variant, have both been associated with re-infections of individuals who previously had COVID-19. Most recently, E484K mutations have also been found in Kent and other places in the UK. The emergence of such cases also in the UK raises concerns that the spread of E484K variants may reduce the protection provided by our current vaccine programmes.

‘We can already see that increased immunity from vaccinations and previous infections causes a selection pressure resulting in new SARS-CoV-2 variants that can bypass this pre-existing protection. Our vaccination efforts will be substantially complicated by this.

‘New variants carrying E484K mutations clearly confirm that vaccination campaigns alone will not solve all our COVID-19 problems and further measures will be required. Only the combination of low COVID-19 numbers and broad vaccination campaigns will enable disease control, as the risk of new variants drops with reduced virus spread and replication.’

Professor Michaelis and Dr Wass run a joint computational/ wet laboratory. Dr Wass is a computational biologist with expertise in structural biology and big data analysis. Prof Michaelis’ research is focused on the identification and investigation of drugs and their mechanisms of action, with a focus on cancer and viruses. With regard to viruses, Prof Michaelis and Dr Wass work on virus-host cell interactions and antiviral drug targets. In the cancer field, they investigate drug resistance in cancer. In collaboration with Professor Jindrich Cinatl (Goethe-University, Frankfurt am Main), they manage and develop the Resistant Cancer Cell Line (RCCL) Collection, a unique collection of 2,000 cancer cell lines with acquired resistance to anti-cancer drugs. They are also interested in meta-research that investigates research practices in the life sciences.