If there’s one coronavirus mutation that keeps scientists awake at night, it’s E484K. The mutation was found in both the South African variant (B1351) and the Brazilian variant (P1), but not in the UK variant (B117). This so-called “escape mutation” made one fear that approved Covid vaccines might not be as effective against these variants. The E484K mutation has now also been found in the UK variant, albeit in only 11 cases.
The coronavirus mutates slowly, accumulating about two single-letter mutations a month in its genome. This rate of change is about half that of influenza viruses. At the start of the pandemic, few scientists were concerned that the coronavirus would mutate into something more dangerous. But in November 2020, that changed quickly when the first “variant of concern” was discovered. The newly discovered variant B117 was associated with the huge rise in cases in the south-east of England and London.
Receptor binding domain
Although all mutations found in emerging variants of the coronavirus should be monitored, scientists are especially interested in mutations that occur in the virus ear protein, specifically in the domain receptor-binding domain section of the protein. ear. This section of the virus gets stuck in our cells and starts the infection. Mutations in the receptor-binding domain can help the virus bind more closely to our cells, making it more infectious.
The immunity we develop against 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 elude or partially evade these antibodies. This is why they are called “escape mutations”. E484K is one of these mutations.
The name of the mutation comes from the position in the RNA strand (virus genetic code) that occurs (484). The letter E refers to the amino acid that was originally found at this site (glutamic acid). IK refers to the amino acid that is now in place (lysine).
Several studies have shown that the E484K mutation prevents antibodies directed at this position from binding to it. However, after an infection or vaccination, we do not produce antibodies targeting only one area of the virus.
We produce a mixture of antibodies each targeted to different areas of the virus. How harmful it is to lose the effect of antibodies targeting this specific region will depend on the confidence of our immune system in antibodies targeting that particular site.
Two studies, one in Seattle and the other in New York, investigated this. In the Seattle study, which is a prepress (i.e., not yet peer-reviewed), the scientists examined the ability of the antibodies of eight people who had recovered from Covid to stop the mutated form of the virus that infects cells, that is, to neutralize the virus.
In samples from three of the individuals, the ability of the antibodies to neutralize the virus was reduced by up to 90% when presented with the mutated form E484K. And it was reduced in samples from one person when presented with a different mutation at the same position. However, the ability to neutralize samples from four of the individuals was not affected by the mutation.
In the New York study, scientists examined the effect of a series 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 challenged with mutations that occur at different positions of the ear protein. This highlights the uniqueness of the antibody response produced by different people.
These two laboratory studies used only a few samples collected from naturally infected people, rather than vaccinated, so the results may vary, as we know that the immunity obtained through vaccination is generally more robust. As a result, several research groups have recently published data, such as prepress, that have examined the impact of this mutation on vaccine-induced protection.
Effect on vaccines
One such study, published by New York scientists, examined the antibodies of 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, examined the antibodies of 20 people vaccinated with the Pfizer / BioNTech vaccine. A third, published by scientists in Cambridge, England, examined five people vaccinated with the Pfizer / BioNTech vaccine.
Both New York and Texas studies showed that while the effectiveness of the vaccine to protect against variants carrying the E484K mutation was slightly reduced for some people, it was still within a level. acceptable. Decreases in antibody neutralization capacity are measured in the “fold change”. As an example, antibodies produced by an influenza vaccine should see a double decrease of more than four before scientists have to alter the vaccine.
The Texas study reported a doubling of 1.48 in antibodies and the New York study reported decreases in folds of one to three. However, the Cambridge study found that the antibodies of three of the five people had a double decrease of more than 4 when challenged with a virus carrying the E484K mutation.
A key difference between the Cambridge and US studies is that US studies used the South African variant, while the Cambridge study introduced the E484K mutation into the UK variant (B117) and the use in your tests. This may indicate that recent reports of the detection of this mutation in B117 should be of more concern to UK health officials than the import and subsequent circulation of the South African variant.
However, it is worth noting that previous studies are based on very small sample numbers and that any conclusions should be drawn with caution.
However, it emphasizes the importance of examining the combined effect of multiple mutations rather than studying only individual ones, as a single mutation is unlikely to lead to a complete flight of natural or immune-derived immunity. vaccine.
Claire Crossan is a researcher in virology at Glasgow Caledonian University.
This article first appeared in The Conversation.