As the world races to put vaccines on the gun, one of the most worrying variants of the coronavirus seems to be getting a little more worrying.
Researchers in the UK have detected at least 15 cases of B.1.1.7 variants carrying an additional mutation: E484K, a mutation already seen in other worrying variants that could make current vaccines less effective in preventing infection. Variant B.1.1.7, first identified in the UK, is already known to spread more easily among people than previous strains of the pandemic coronavirus SARS-CoV-2. And according to some preliminary evidence, it can cause more serious illnesses.
So far, variants B.1.1.7 with E484K seem rare. On Monday, Public Health England reported in a technical briefing that it detected E484K in just 11 B.1.1.7 variants among more than 200,000 viruses examined. For now, it is not clear whether the enlarged mutants will take off and become dominant in the population or disappear. It is also not entirely clear what the addition of E484K means to B.1.1.7 in people. Preliminary laboratory experiments suggest that the mutation alone, and its presence in B.1.1.7 specifically, may help the virus to escape immune responses. However, further studies and clinical data are needed to understand the full effect of the new addition.
Still, without a doubt, the new mutation in B.1.1.7 signals again that the pandemic coronavirus has not stopped trying to deceive us, even though several vaccines prove that they can prevent infections and prevent serious diseases. As long as we continue to allow the virus to spread wildly among us, the virus will have ample opportunities to enhance its ability to cause disease and prevent vaccines – and will use them. The findings again highlight that we must continue to use proven mitigation efforts – physical distance, wearing a mask, hand hygiene, good ventilation and avoiding crowds and closed areas – to reduce transmission as much as possible while vaccination efforts are underway. progress.
In fact, given the current state of the pandemic and what we already know about the virus, some researchers say that finding E484K in B.1.1.7 is hardly surprising. It may have been just a matter of time.
Variants
B.1.1.7 made headlines worldwide for the first time in early December, after UK researchers saw an increasing number of cases in a matter of weeks. Other data and analysis supported the initial fear that it seems to spread more easily among people. Although the research is ongoing, some estimates say it is about 50 percent more transmissible than previous SARS-CoV-2 strains. Since then, it has been found in more than 70 countries, including the United States. The US Centers for Disease Control and Prevention estimates that B.1.1.7 may become the dominant strain in the country in March.
The fast-spreading variant was found for the first time with 23 mutations, three of which are of particular concern. All three are in the virus’s spike protein, the club-like proteins that project from the virus’s spherical particle. The virus uses its spines to cling and enter cells, thus initiating an infection. At least two of the peak mutations in B.1.1.7, including the notorious N501Y, are believed to help the virus enter cells more easily.
While B.1.1.7 was invading the United Kingdom, two other worrying variants were emerging in the southern hemisphere: the 501Y.V2 / B.1.351 variant identified in South Africa and the P.1 variant identified in Brazil. Both variants are feared to avoid the immune responses that follow infections with previous strains of the virus or current vaccines, which means that people vaccinated or recovered from COVID-19 may still be vulnerable to infection by the variants. And both variants carry the E484K mutation in their spike protein.
The mutation is in a critical peak area, called the receptor-binding domain, or RBD. RBD is the area of the peak that – as the name implies – binds directly to a protein receptor in human cells, called ACE2. The connection of Spike’s RBD to ACE2 is what initiates an infection. With this fundamental role, RBD is the main target of the most potent antibodies, called neutralizing antibodies. If an antibody attaches to the RBD, it can prevent the virus from binding to ACE2 and infecting cells. On the other hand, mutations in RBD can eliminate antibodies, weakening the once potent immune responses.
Mutation mashup
Preliminary laboratory studies have suggested that mutations in the RBD protein code at amino acid position 484 were the best to avoid antibodies from people who recovered from COVID-19. The specific mutation E484K – transforming a glutamic acid (E) at position 484 into lysine (K) – decreased the potency of the antibodies ten times. The researchers observed similar drops in neutralizing potency when they confronted the peak E484K proteins against antibodies from people vaccinated with either of the two mRNA vaccines currently authorized in the United States (vaccines from Moderna and Pfizer / BioNTech).
Likewise, some very preliminary data – from a peer-reviewed study with significant caveats – suggests that adding the E484K mutation to the B.1.1.7 peak protein may mean that current vaccines will be less effective. The study used blood with antibodies taken from people who received only the first of two doses of the Pfizer / BioNTech mRNA vaccine. As before, the presence of E484K meant that much higher antibody levels were needed to neutralize the virus. It is important to note, however, that antibody levels would be higher after the second dose of the vaccine.
The good news about all this is that both mRNA vaccines are highly effective (about 95 percent) in preventing COVID-19. Even with reductions in the effectiveness of cunning variants, experts hope that – for now – vaccines are still protective, particularly against serious illnesses. But the fact that E484K has now emerged in each of the three most worrying variants of the coronavirus suggests that the mutation offers some advantage. And the virus will continue to gain these advantages as long as we allow it to spread.