If there’s one coronavirus mutation that keeps scientists awake at night, it’s E484K. The mutation was found in both the South African version (B1351) and the Brazilian version (P1), but not in the United Kingdom version (B117). This so-called “escape mutation” has raised fears that approved Covid vaccines may not be as effective against these variants. The E484K mutation has now been found in the UK version – albeit in only 11 cases.
The coronavirus moves slowly, accumulating around two single-letter mutations per month in its genome. This rate of change is about half that of influenza viruses. At the beginning of the pandemic, few scientists were worried that the coronavirus would turn into something more dangerous. But in November 2020, this changed rapidly when the first “option of concern” was discovered. The newly discovered variant B117 has been associated with the huge increase in cases in the south-east of England and London.
Receptor binding domain
While all mutations found in emerging variants of coronavirus should be monitored, scientists are particularly interested in mutations that occur in the virus’s spike protein, especially the spike receptor binding domain section. This section of the virus gets stuck in our cells and initiates the infection. Mutations in receptor binding can help the virus bind more closely to our cells, making it more infectious.
The immunity we develop to coronavirus, after vaccination or infection, is largely due to the development of antibodies that bind to the receptor binding domain. Mutations in this region may allow the virus to evade or partially evade these antibodies. This is why they are called “escape mutations”. E484K is such a mutation.
The name of the mutation comes from the position in the RNA string (the genetic code of the virus) that it has (484). The letter E refers to the amino acid that was originally in this location (glutamic acid). And K refers to the amino acid that is now in that location (lysine).
Several studies have shown that the E484K mutation stops antibodies targeting this position from binding to it. However, after an infection or vaccination, we do not produce antibodies that target only one area of the virus.
We produce a mixture of antibodies, each targeting different areas of the virus. How harmful the loss of the effect of antibodies targeting this specific region is will depend on how much our immune system relies on antibodies targeting this particular site.
Two studies, one in Seattle and the other in New York, investigated this. In the Seattle study, which is a prepress (meaning it’s not yet evaluated by colleagues), scientists examined the ability of antibodies from eight people who recovered from Covid to stop the mutant form of infecting cells. virus – in other words to neutralize the virus.
In samples from three of the people, the ability of the antibodies to neutralize the virus was reduced by up to 90% when presented with the mutant form E484K. And it was reduced to samples from a single person when it showed a different mutation in the same position. However, the ability to neutralize samples from four of the people was not affected by the mutation.
In the New York study, scientists examined the effect of a range of mutations on the ability of antibodies, collected from four people, to neutralize the virus. The researchers found that none of the antibodies were affected by the E484K mutation.
However, two of the samples saw a reduction in the ability to neutralize when caused by mutations that occur at different positions in the protein spike. This highlights the uniqueness of the antibody response produced by different people.
Both laboratory studies used only a few samples collected from people who were naturally infected, as opposed to those vaccinated, so the results may differ because we know that the immunity obtained by vaccination is generally more robust. As a result, several research groups have recently published data, as preprints, examining the impact of this mutation on vaccine-induced protection.
Effect on vaccines
One of these studies, published by New York scientists, looked at antibodies from 15 people vaccinated with either of the two approved mRNA-based vaccines (those produced by Pfizer / BioNTech and Moderna).
The second, published by Texas scientists in collaboration with Pfizer, analyzed antibodies from 20 people vaccinated with the Pfizer / BioNTech vaccine. A third, released by scientists in Cambridge, England, analyzed five people vaccinated with the Pfizer / BioNTech vaccine.
Both New York and Texas studies have shown that while the effectiveness of the vaccine in protecting against variants carrying the E484K mutation has been slightly reduced for some people, it was still at an acceptable level. Decreases in the ability to neutralize antibodies are measured in “fold change”. For example, antibodies produced by an influenza vaccine should decrease more than four times before scientists have to change the vaccine.
The Texas study reported a 1.48 drop in antibodies, and the New York study reported one- to three-fold decreases. However, the Cambridge study found that antibodies from three of the five people had a 4-fold decrease when they were provoked with a virus carrying the E484K mutation.
A key difference between the Cambridge and US studies is that the US studies used the South African version, while the Cambridge study introduced the E484K mutation into the British version (B117) and used it in their tests. This may indicate that recent reports of this mutation in B117 should be more worrying for UK health officials than the subsequent import and circulation of the South African variant.
However, it is worth noting that the above studies are based on a very small number of samples and any conclusions should be drawn with caution.
However, it emphasizes the importance of examining the combined effect of multiple mutations, as opposed to studying only individual mutations, as a single mutation is unlikely to lead to a complete escape from natural or vaccine-derived immunity.
Claire Crossan is a virology researcher at Glasgow Caledonian University.
This article first appeared on The Conversation.