As new variants of the coronavirus that causes COVID-19 emerge, a number of new studies suggest that some could elude immune responses triggered by a previous infection or by a vaccine. That concern has already led some vaccine manufacturers to look for ways to adjust their shots to keep up with these troubled newcomers.
The researchers were concerned that mutations in a viral protein that helps the coronavirus break down in cells could dampen the immune response against the virus. New studies suggest that some viral variants may escape at least some of that immunity, which could put people at risk for infection who have been vaccinated or have already recovered from a COVID-19 attack (SN: 24/08/20).
Still, “we should urge caution, but not panic,” says Mark Slifka, a microbiologist and immunologist at Oregon Health & Science University in Portland. “The immune system has multiple backups” to deal with constantly changing viruses, he says.
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What’s more, it should be easy – at least in principle – to update vaccines that depend on parts of the coronavirus genetic code to trigger an immune response (SN: 7/10/20). And while some virus mutations can damage the proper functioning of vaccines, currently authorized cows have a long way to go before they can be ineffective, Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases and senior medical advisor President Biden said in a January 21 briefing.
COVID-19 vaccines developed by Pfizer and Moderna have been shown to be very effective in clinical trials (SN: 18/12/20), with an efficacy of approximately 95 percent. The U.S. Food and Drug Administration recommends that COVID-19 vaccine candidates have an effectiveness of at least 50 percent for emergency use authorization (SN: 10/4/20).
Mixture of mutations
Viruses mutate all the time and the coronavirus that causes COVID-19 is no exception (SN: 26/05/20). Although most changes have little or no effect on the behavior of the virus when it infects a person, some rare alterations can make some viral variants more dangerous to people, such as making a virus more transmissible or deadly.
Another danger can arise if a mutation helps the virus bypass the body’s immune response. Protection against any virus comes, in part, in the form of immune proteins called antibodies, which bind to the proteins in the virus. Immune proteins can prevent the virus from entering other cells or stimulate the action of other immune cells. Mutations in viral proteins can weaken or prevent such binding, making the antibody response less effective.
These problematic mutations are now appearing in some versions of the coronavirus that researchers are tracking. A virus variant called B.1.1.7, first identified in the UK, appears to be more transmissible than its close relatives, giving it a potential evolutionary advantage (SN: 22/12/20). Researchers are also monitoring the spread of a variant in South Africa called 501Y.V2 that has some of the same mutations as B.1.1.7, as well as other changes. Another potentially worrying variant called P.1 has emerged in Manaus, Brazil, a region that has already been hit hard by the pandemic in 2020 (SN: 24/09/20).
The South African variant has not yet been detected in the United States. But the UK variant, which is already circulating in 24 states, could become the country’s dominant strain in March (SN: 15/1/21). And the first American case of the Brazil variant was reported on January 25 in someone who had traveled to the South American country.
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Vaccines against variants
Researchers have investigated how these variants might respond to vaccines and some versions of the coronavirus are more worrisome than others.
In the case of B.1.1.7, for example, a serum containing antibodies taken from the blood of 23 people who had received the Pfizer vaccine may still prevent the variant from infecting human cells in laboratory dishes, researchers said in a preliminary study published on January 20th. at medRxiv.org. However, that immune response to B.1.1.7 was lower in some samples compared to a version of the new coronavirus that does not have these mutations. Another preliminary study published on January 19 on bioRxiv.org found that the immune responses of the Moderna vaccine were similar to those of Pfizer against the new variant.
However, some data on the 501Y.V2 variant of coronavirus are more worrisome. Antibodies in the serum of 21 out of 44 people who recovered from COVID-19 lost the ability to neutralize the new viral variant in laboratory-cultured cells, the researchers report in a preliminary study published Jan. 19 at bioRxiv.org.
A small separate preliminary study of six recovered patients found that those people’s antibodies had a wide range of abilities to fight viruses, according to researchers Jan. 26 at medRxiv.org. A person’s antibodies completely lacked the ability to prevent 501Y.V2 from infecting cells. The other five people had antibodies between six and two hundredths of potent against 501Y.V2 as against the coronavirus version behind the first South African wave of COVID-19.
However, early results also suggest that the Modern vaccine should work against B.1.1.7 and 501Y.V2, researchers reported on Jan. 25 in a preliminary study published on bioRxiv.org.
The team took blood samples from eight people who had received the Modern vaccine in a phase I clinical trial and then tested the samples on lab plates to see if the new virus variants could still infect the cells. The immune response to B.1.1.7 and to a coronavirus variant that did not have the potentially problematic mutations was similar. But it was only a sixth so effective at preventing 501Y.V2 from entering the cells.
Still, that level of activity is robust enough to protect monkeys from developing COVID-19l when exposed to a different version of the coronavirus, Moderna reported in a Jan. 25 press release. This suggests that although vaccine-induced immunity has decreased compared to 501Y.V2, vaccinated individuals may still have some level of protection against the new variant. It is possible that people who recovered from a previous attack of COVID-19 and whose antibody levels had decreased may be more susceptible to reinfection with 501Y.V2 than other variants.
“These reports are worrisome,” says Nina Luning Prak, an immunologist at the University of Pennsylvania. Still, he says, "you have several shots on goal." People make a myriad of antibodies that attack many different parts of a viral target, making it difficult for a virus to escape all at once (SN: 14/01/21).
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The researchers focused primarily on neutralizing antibodies, which prevent viruses from infecting host cells, and in the first place, can prevent a viral infection. While antibodies from 21 recovered patients could no longer prevent the variant from entering cells in the January 19, 501Y.V2 bioRxiv.org study, other antibodies were still bound to the virus but did not neutralize it.
Slifka says in the body that these non-neutralizing antibodies could activate other immune cells to eliminate the coronavirus. In addition, people who have recovered from infections have long-lasting immune cells that stick to the blood and produce antibodies if a person becomes exposed to the coronavirus again. These cells can produce antibodies that can even bind to mutated viruses (SN: 24/11/20).
Experts still don’t know what metrics, such as antibody levels in the blood, indicate if a person is protected against coronavirus. This makes it difficult to know from experiments done with cells cultured in the laboratory whether low levels of neutralizing antibodies are enough to stop an infection in a person or protect them from the development of severe COVID-19, says Stuart Ray, virologist and doctor of infectious diseases in medical school. of Johns Hopkins University.
Response from vaccine manufacturers
Although preliminary results hint at some problems for vaccines, there is still not enough evidence to push scientists to start giving people updated shots. To do that, “I think we would have to see evidence of reinfections in people who have well demonstrated immune responses” to the coronavirus, Ray says.
If it got to that point, some types of vaccines might be easier to upgrade than others. A new version of mRNA vaccines like Pfizer and Moderna could be made in the lab in a few days, says John Mascola, director of the DIA Vaccine Research Center and Betty Bumpers at NIAID. Moderna announced on January 25 that the company plans to conduct clinical trials to test whether vaccinated people could get a third dose of their vaccine. Modern also plans to test a booster shot that uses a coronavirus variant protein in South Africa. Pfizer said the company is preparing the groundwork to adjust its vaccine.
Other vaccines, such as AstraZeneca or Johnson & Johnson, need to be produced in cells grown in the laboratory, which can take a few weeks (SN: 23/11/20). Companies would have to increase manufacturing by millions of doses, which takes time.
But one of the complications is how regulatory agencies like the FDA may want to test up-to-date vaccines to adjust for new coronavirus variants. So far, it’s unclear. If experts learn that signs of the immune system correlate with immunity in ongoing clinical trials, new vaccines could be tested in tens or hundreds of people, as agencies for upgraded flu vaccines already do, instead of tens of thousands . But for now, says Mascola, "it's an unknown territory."