SOON after vaccination began in many countries, reports of faster-spreading coronavirus variants triggered fears that vaccines might not protect against them. The good news is that initial studies suggest that the existing shots will still work, although they might be slightly less effective against two variants, one that emerged in South Africa and one from Brazil.
“I am optimistic that current vaccines will remain quite useful,” says Jesse Bloom at the Fred Hutchinson Cancer Research Center in Seattle. “But I do expect that eventually it will be necessary to update vaccines to account for viral evolution.”
Antibodies are our main defence against viruses. When we get infected by a new virus, our immune system starts producing a range of antibodies that bind to various parts of viral proteins.
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Not all antibodies are equal. Studies show that only a few antibodies can “neutralise” viruses and prevent infections. These neutralising antibodies bind to key sites on viral proteins.
For the coronavirus, one such site is the part of its so-called spike protein that binds to receptors on human cells and helps the virus get inside – the receptor binding domain. If this part of the spike protein changes, neutralising antibodies may not bind as well.
A rapidly spreading variant named B.1.1.7, first spotted in the UK, has only one mutation that affects this binding domain. Initial studies of antibodies from those previously infected by the coronavirus or given the Pfizer and BioNTech vaccine show against B.1.1.7.
The variant from South Africa, called B.1.351, is of more concern. It has three mutations in the binding domain, including one named E484K as it occurs at a site called E484. The variant from Brazil, known as P.1, has almost the same three mutations.
According to a , B.1.351’s spread can be explained by this variant being 50 per cent more transmissible or 20 per cent better at evading immunity in previously infected people, when compared with previous variants. Lab studies point to the latter.
Bloom and his team how mutations in the binding domain alter the effectiveness of antibodies from people who have been infected with the coronavirus. Mutations at the E484 site made the biggest difference, with neutralising activity falling as much as tenfold.
While that sounds alarming, current vaccines work so well that even a big drop in neutralisation might not substantially reduce protection, says Bloom. The antibodies might not be as effective, but they still get the job done. There were also differences between individuals: antibodies from some worked just as well.
“A mutation in the variants from Brazil and South Africa may help the virus evade antibodies”
More evidence comes from a study by Rino Rappuoli at GlaxoSmithKline Vaccines in Italy. When his team grew the virus in the presence of antibodies from a previously infected person, E484K was that let the virus become resistant.
These findings suggest that the spread of B.1.351 and P.1 is due to the E484K mutation helping the virus evade antibodies and reinfect people who have already had covid-19. “Whether on top of this they are more infectious, I don’t know,” says Rappuoli.
There have been reports of reinfections in South Africa, government epidemiologist Salim Abdool Karim said in an online presentation. There has also been a report of a woman in Brazil having more severe symptoms the second time round. But such anecdotal reports are to be expected, said Karim, and in South Africa there is no evidence of a systematic rise in reinfections.
This could be because testing how well antibodies neutralise viruses outside the body doesn’t tell the whole story. The so-called T-cell response is also important. T-cells spot an infected cell by detecting viral proteins on its surface, and then destroy it before it releases more viruses.
“T-cells can be incredibly valuable at preventing disease,” says Shane Crotty at the La Jolla Institute for Immunology in California. “They can do it so well that the person never gets sick.”
Crucially, an effective T-cell response only requires the recognition of viral proteins, rather than the blocking of their function. This means it is harder for resistance to evolve because no one site is crucial.
The T-cell response to the coronavirus is broad, involving many parts of the spike protein as well as other proteins. “There is no way these variants are escaping T-cell immunity,” says Crotty. Unfortunately, while T-cells can stop people getting symptoms, they cannot prevent infections.
Escape variants
The bottom line is that existing vaccines should still protect against B.1.351 and P.1, but might be slightly less effective. And there is a danger of these variants or others evolving to be much better at evading vaccine protection.
This means we need to step up surveillance so we can spot any such “escape variants” early and have time to update vaccines, says Angela Rasmussen at Georgetown University in Washington DC.
“It is unlikely that, overnight, a variant is going to emerge that is capable of completely evading the vaccine,” she says. “But if we are not looking, then we might not find them until it’s too late.”
żěè¶ĚĘÓƵs are already looking at how to update the vaccines and it will be relatively easy to update most of them. The main delay could be getting them approved. żěè¶ĚĘÓƵ asked regulators in the UK, US and Europe what manufacturers would need to do.
None has yet decided on the process, but some pointed to the updating of seasonal flu vaccines as a possible precedent. Updated flu vaccines don’t have to undergo clinical trials, so the process could be rapid. “I believe it can be done very quickly,” says Rappuoli.
