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All viruses undergo random mutations in their genetic material. Any change that offers a benefit – such as causing the virus to infect more hosts or to resist certain drugs – will tend to be favored as long as it does not also create a disadvantage, such as slower replication of the virus.
The speed with which a given virus mutates can have a big impact on how well vaccines work, if at all. Influenza viruses change genes quickly, which is why we need a new vaccine every year. And there is still no vaccine against HIV, the virus that causes AIDS, in part because HIV mutates extremely quickly.
The coronavirus is several orders of magnitude less inconstant. “There is more viral diversity in a single individual infected with HIV than in the entire population worldwide with covid-19,” says Michael Farzan, a biologist at Scripps Research in Jupiter, Florida. “If I found the most divergent versions of SARS-CoV-2 that exist, one from China in 2019 and one from Maine in 2020, they would be less different than what you see in an HIV-positive person.”
The coronavirus has a comparatively large genome – around 30,000 letters, three times as many as in HIV or the flu virus – and it changes much less quickly.
In addition, the spike protein is a fairly large structure, made up of around 1270 amino acids. This gives the body’s immune system a wide target; it generates many different antibodies against different parts of the tip. Moderna and Pfizer / BioNTech’s vaccines both trigger this “polyspecific” immune response. A single mutation of the peak, or even a few, shouldn’t make them much less effective. The UK variant, for example, includes nine tip gene mutations, but remains 99% identical to the version that vaccines can neutralize.
“We know this virus is not stable. No virus is stable. This virus is evolving, ”said Uğur Şahin, founder and CEO of BioNTech, during a press conference December 22 in Germany. “But there are a lot more sites that are not being transferred.” Şahin said that over the past month, whenever a new mutation has appeared, the company’s lab tests have shown that the vaccine should still be effective. BioNTech has verified around 20 to date and plans to run the same tests with the UK variant. This experiment will take two weeks, but Şahin says that “scientifically it is very likely” that the vaccine still works.
Likewise, Moderna, which began distributing its vaccine in the United States this week, said it believed “the vaccine-induced immunity would be protective against the variants recently described in the United Kingdom.” Eli Lilly, who makes an anti-covid-19 antibody, said he had already tested it against the main mutation seen in the British variant, and that it still works.
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Still, some researchers say the mutations will eventually make current vaccines and treatments less effective. “This tells me that we are going to need another version of the vaccine. I am convinced of it, ”says Farzan. “We’re going to follow these variations like we do the flu.”
If updated vaccines are needed, it could strongly favor the technology behind Moderna and Pfizer / BioNTech’s vaccines, both of which are already licensed in the United States. They use the genetic data of the coronavirus, in the form of messenger RNA (mRNA), to prime the body’s immune system. The vaccine is essentially a container containing the RNA, so that when a new variant of the virus appears, the corresponding RNA can simply be replaced.
“Technically, it is possible to make a new vaccine mimicking the new strain in a matter of weeks,” Şahin said at the press conference.
Moderna’s initial vaccine doses, for example, were manufactured last February, just one month after China first disclosed the coronavirus genome.
“That’s why people buy stocks in mRNA companies,” Farzan says. “These are the guys who will have the fastest response on the second go-around.”
And what about drugs?
While companies say vaccines are not easily affected by a few mutations, the two antibody drugs licensed in the US so far are less flexible. This is because while a vaccine causes the immune system to make a large number of different antibodies, antibody drugs contain only one or two particularly strong antibodies.
At present, however, the makers of these drugs are also optimistic.
Bamlanivimab, the medicine sold by Eli Lilly, is based on a antibody found in one of the first patients with covid-19 in the United States. The drug is given by injection to people with moderate covid-19 and was cleared in November. Former New Jersey governor Chris Christie received drug after catching covid-19 while US president Donald Trump received similar antibody treatment from Regeneron Pharmaceuticals.
Since the Lilly antibody targets a location on the receptor binding domain, the hot spot on the peak, any mutation in this region – such as the N501Y mutation seen in the UK – could make the drug less effective. But Ajay Nirula, vice president of immunology at Eli Lilly, wrote in an email that the company’s testing “suggests that bamlanivimab should maintain full activity against the new strain.”
Likewise, Regeneron said they were not worried about the UK variant. His treatment includes two antibodies, which bind to different parts of the spike protein, making it more difficult for the drug to be deactivated by a chance mutation in the virus.
“Everything we know so far about this variant and our antibodies – including data from preliminary neutralization analyzes and against other variants currently in circulation – indicates that our cocktail will remain effective against this new strain,” said said Alexandra Bowie, spokesperson for Regeneron.
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