As the world races to get vaccines into arms, one of the most concerning coronavirus variants appears to be getting a little more concerning.
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 concerning variants and one that may make current vaccines less effective at preventing infection. The B.1.1.7 variant, first identified in the United Kingdom, is already known to spread more easily among people than earlier strains of the pandemic coronavirus SARS-CoV-2. And according to some preliminary evidence, it may cause more severe disease.
So far, B.1.1.7 variants carrying E484K appear rare. On Monday, Public Health England reported in a technical briefing that it had detected E484K in just 11 B.1.1.7 variants among more than 200,000 viruses examined. For now, it’s unclear if the augmented mutants will take off and become dominant in the population or fizzle out. It’s also not entirely clear what the addition of E484K means for B.1.1.7 in people. Preliminary laboratory experiments suggest the mutation alone, and its presence in B.1.1.7 specifically, may help the virus evade immune responses. But more studies and clinical data are necessary to understand the full effect of the new addition.
Still, without doubt, the new mutation in B.1.1.7 signals again that the pandemic coronavirus is not done trying to outwit us, even as numerous vaccines prove they can thwart infection and prevent severe disease. As long as we continue to let the virus spread rampantly among us, the virus will have ample opportunities to hone its disease-causing and vaccine-evading capabilities—and it will use them. The findings highlight once again that we must continue to use proven mitigation efforts—physical distancing, mask wearing, hand hygiene, good ventilation, and avoiding crowds and enclosed areas—to reduce transmission as much as possible while vaccination efforts are underway.
In fact, given the current state of the pandemic and what we know about the virus already, some researchers say finding E484K in B.1.1.7 is not at all surprising. It may have just been a matter of time.
Variants
B.1.1.7 first made global headlines in early December after UK researchers watched it make up larger and larger proportions of cases there over a matter of just weeks. Further data and analyses backed up the initial fear that it does seem to spread more easily between people. Though research is ongoing, some estimates peg it as being around 50 percent more transmissible than the earlier SARS-CoV-2 strains. It has since 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 predominant strain in the country in March.
The fast-spreading variant was first found carrying 23 mutations, with three particularly worrisome ones. The three are in the virus’ spike protein, the characteristic club-like proteins that jut from the virus’ spherical particle. The virus uses its spikes to latch onto and enter cells, thereby initiating an infection. At least two of B.1.1.7’s spike mutations, including the notorious N501Y, are thought to help the virus enter cells more easily.
While B.1.1.7 was invading the UK, two other concerning variants were up and coming 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 evade immune responses that follow infections with earlier strains of the virus or from current vaccines, meaning 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 sits in a critical area of spike, called the receptor binding domain, or RBD. The RBD is the area of the spike that—as the name implies—directly binds to a protein receptor on human cells, called ACE2. Spike’s RBD binding to ACE2 is what starts an infection. With such a key role, the RBD is a prime target of the most potent antibodies, called neutralizing antibodies. If an antibody gloms on to the RBD, it can keep the virus from binding ACE2 and infecting cells. Conversely, mutations to the RBD can throw antibodies off, making once-potent immune responses wimpy.
Mutation mashup
Preliminary lab studies suggested that mutations to the RBD’s protein code at amino acid position 484 were the best at dodging antibodies from people who had recovered from COVID-19. The specific mutation E484K—turning a glutamic acid (E) at position 484 to lysine (K)—lowered the potency of antibodies tenfold. Researchers saw similar drops in neutralizing potency when they pitted E484K-toting spike proteins up against antibodies from people vaccinated with either of the two mRNA vaccines currently authorized in the United States (vaccines by Moderna and Pfizer/BioNTech).
Likewise, some very preliminary data—from a not-yet peer-reviewed study with significant caveats—suggests that the addition of the E484K mutation to B.1.1.7’s spike protein may mean current vaccines will be less effective. The study used antibody-toting blood drawn from people given just the first of two doses of the Pfizer/BioNTech mRNA vaccine. As before, the presence of E484K meant that it took much higher antibody levels to neutralize the virus. It’s important to note, however, that antibody levels would be higher after the second dose of the vaccine.
Some good news in all of this is that both mRNA vaccines are highly effective (around 95 percent) at preventing COVID-19. Even with reductions in efficacy from wily variants, experts expect that—for now—the vaccines will still be protective, particularly against severe disease. But the fact that E484K has now arisen in each of the three most concerning coronavirus variants suggests that the mutation offers some advantage. And the virus is going to keep gaining such advantages as long as we allow it to spread.
https://arstechnica.com/?p=1739212