Will new mutations now out there make vaccines les

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s scientists try to track the spread of a new, more infectious coronavirus variant around the world — finding more cases in the United States and elsewhere this week — they are also keeping an eye on a different mutation with potentially greater implications for how well Covid-19 vaccines work.

The mutation, identified in a variant first seen in South Africa and separately seen in another variant in Brazil, changes a part of the virus that your immune system’s antibodies get trained to recognize after you’ve been infected or vaccinated. Lab studies show that the change could make people’s antibodies less effective at neutralizing the virus. The mutation seems to help the virus disguise part of its signature appearance, so the pathogen might have an easier time slipping past immune protection.

It’s not that the mutation will render existing vaccines useless, scientists stress. The vaccines authorized so far and those in development produce what’s called a polyclonal response, generating numerous antibodies that home in on different parts of the virus. Changes to any of those target sites raise the possibility that the vaccines would be less effective, not that they won’t work at all.

“With one mutation or even three mutations, it’s expected the antibodies will still recognize this variant, though they might not recognize it as well as other variants,” said Ramón Lorenzo-Redondo, a molecular virologist at Northwestern University’s Feinberg School of Medicine.

Essentially, the mutation is getting attention because it appears more likely to have some effect on vaccines than other mutations that have emerged, though scientists are still trying to test that hypothesis. The more contagious variant raising global alarms, which was first seen in the United Kingdom and is referred to as B.1.1.7, is not thought to have mutations that will greatly affect vaccines, the evidence so far indicates.

“We need to be monitoring for these mutations,” said Jesse Bloom, an evolutionary virologist at Fred Hutchinson Cancer Research Center, who with colleagues published a paper about this specific mutation, known as E484K, this week.

But Bloom added that he believed the virus would have to pick up multiple mutations — and particular mutations in specific spots, not just any alterations — to have a serious effect on vaccine efficacy, which will likely take some time.

“I’m quite optimistic that even with these mutations, immunity is not going to suddenly fail on us,” Bloom said. “It might be gradually eroded, but it’s not going to fail on us, at least in the short term.”

Scientists do think the coronavirus could eventually change so much that the immunity provided by vaccines will be threatened, a process that will pick up as the number of people protected from the virus — either through vaccination or infection — grows and evolutionary pressure in turn increases. But they still anticipate it could take years, and that when it does occur, vaccine makers can tweak their designs to match the newer variant, a process some companies have said would only take weeks.

The SARS-CoV-2 coronavirus, which causes Covid-19, has been mutating as it spreads, just like other viruses. Many of the mutations do nothing, and some might even impede the virus’s quest to replicate and spread. But every so often, a random mutation gives the virus an evolutionary advantage, and that variant can then become dominant. Early on in the pandemic, a mutation known as D614G helped the coronavirus spread more easily, and variants with that mutation quickly overtook others globally.

B.1.1.7, which has since spread to other parts of the world, appears to be even more infectious, with some estimates saying it’s 50% more transmissible. One of its mutations, called N501Y, improves how well the virus’ spike protein can attach to a receptor called ACE2 on human cells, making it more likely for the virus to successfully infect cells and for the virus to pass from person to person.

The same N501Y mutation is also present in the variant identified in South Africa, though the two variants evolved independently. (Public health authorities are trying to steer people away from using terms like the “U.K. variant” or “South African variant,” just as they discourage people from tying SARS-2 by name to China or Wuhan. “We need to use the names appropriately because we don’t want to stigmatize where these variants have been identified,” the World Health Organization’s Maria Van Kerkhove said Tuesday. “That’s true for any virus that’s identified.”)

The inclusion of N501Y appears to help the variant in South Africa spread faster as well, but the variant also has the E484K mutation, unlike the variant that first appeared in the U.K. Though mutations in the same part of the virus have cropped up previously during the pandemic, the specific E484K mutation is attracting more interest now in part because it’s in this variant that’s spreading across South Africa and, through travelers, has started to appear elsewhere, including Japan, Norway, and the U.K.

The E484K change occurs on a part of the spike protein called the receptor binding domain, which plays a crucial role as the virus attaches to ACE2 and is a key target for antibodies. As lab studies have shown, antibodies don’t recognize variants with E484K as well as other forms.

Research from Bloom and colleagues this week further added to that evidence. In their study, which involved mapping how antibodies from people who had recovered from Covid-19 fared against different variants, the scientists found that mutations like E484K had the biggest impact on antibodies’ ability to block the virus, with some people experiencing a more than 10-fold drop in neutralization against the variant. The researchers called the location of the E484K mutation “the site of most concern for viral mutations.” (There was variability among the samples, however; some people were able to neutralize the variant just fine, and mutations in other places had more of an impact than E484K did for certain people.)

Bloom’s study was focused on people who had recovered from an infection, not those who had been vaccinated; researchers around the world are investigating how well current vaccines stand up to different variants.

But despite what he and colleagues found about E484K, Bloom noted that the mutation only reduced neutralizing activity, and didn’t eliminate it. Current vaccines, meanwhile, have shown they can generate strong immune responses. “I’m confident current vaccines will be useful for quite a while,” Bloom wrote in a Twitter thread detailing the research.

The more pressing concern for now, scientists say, remains the spread of B.1.1.7, the variant first seen in the U.K. Though it’s not thought to cause more severe cases of Covid-19, if it causes more cases overall because it spreads more easily, that will lead to more hospitalizations and deaths. It is also likely harder to control than other variants and raises the threshold of the percentage of the population that needs to be protected to reach herd immunity.

“The variant is a really big deal,” said Marc Lipsitch, an epidemiologist at Harvard’s T.H. Chan School of Public Health.

Lipsitch said the U.S. should focus its efforts on curtailing the variant, including by sequencing more samples from patients to identify cases and directing its contact tracing and quarantining campaigns to try to hem it in.

“To the extent that we can find those and preferentially stop the spread, it won’t be perfect, it will be far from perfect, but anything we can do to delay the spread of this new variant virus will make control easier and will help us in the race to get more people vaccinated before this becomes more common,” he said.
About the Author Reprints
Andrew Joseph

General Assignment Reporter

Andrew is a general assignment reporter.
andrew.joseph@statnews.com
@DrewQJoseph

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