The increase in COVID-19 cases, the slow deployment of the vaccine, and the emergence of more transmissible coronavirus variants in some countries have sparked debate among scientists about how best to protect people with recently authorized vaccines.
One idea involves delaying when people receive the second of the two required vaccine doses, so that more people can receive the currently available doses.
This is happening in the UK, where researchers have raised concerns about a new variant of coronavirus that appears to be more contagious than other versions. Officials there choose to extend the time between each dose of vaccine from three or four weeks to three months (SN: 22/12/20).
In the United States, meanwhile, officials strongly recommend that states adhere to the regime the U.S. Food and Drug Administration authorized in December: two separate three-week shots for the Pfizer-BioNTech vaccine and four weeks for the Modern.
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On January 12, the Trump administration announced that it would no longer stop the second shots of COVID-19 vaccines, several days after President-elect Joe Biden suggested he would release all shots. While this may speed up the protection of more Americans, it also increases the chance that people may not receive their second doses on time if manufacturing problems arise.
The possibility that second doses may be delayed has some experts worried because it could lead millions of people to walk with only partial immunity to the coronavirus, a condition that could be ripe for harmful mutations of the virus to arise.
Delaying the second shot is a gamble, says Ramon Lorenzo-Redondo, a virologist at Feinberg School of Medicine at Northwestern University in Chicago, especially without much evidence to suggest how well a dose works. Officials “should not throw away (their) best tools” to fight the pandemic, he says. "We don't want to feed (potential viral evolution) by doing a suboptimal immunization of the population."
How it could feed on the evolution of the virus reaches the immune system. If people have complete immunity as a result of vaccination, their immune response is likely to be robust, generating large amounts of neutralizing antibodies, for example, that prevent viruses from entering cells and prevent harmful mutations before they appear. But if people have partial immunity, that immune response is likely to be weaker.
It’s like when doctors encourage patients to complete a full course of antibiotics, Lorenzo-Redondo says. In that case, eliminating susceptible bacteria with a full course could help decrease the chance of pursuers accumulating resistance.
For the COVID-19 vaccine, if people’s second doses are delayed long enough, similar to not completing a full complement of antibiotics, it is possible that a low number of neutralizing antibodies triggered by a single dose can only partially fight an infection. This can provide more time for variants of the virus to emerge and thrive with mutations that bypass the immune system and are transmitted to other people.
If immune dodging variants arise as a result of shooting delays and spread to many people, that could be a blow to vaccine effectiveness. For example, if mutations arose that prevented vaccine-induced antibodies from binding to the virus or caused antibodies to bind with less strain, it is possible that that virus variant infects cells than variants without the mutation, and therefore cause disease, says Lorenzo-Redondo. . With the increase in cases in many places, including the UK and the US, the coronavirus could be even more likely to accumulate vaccine-preventing mutations than it would if the number of cases were lower.
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For now, it is unclear how vaccinated people are protected after a single shot and for how long. Participants in the trial who received the Pfizer-BioNTech vaccine had low levels of neutralizing antibodies 21 days after the first dose, the researchers reported in the Dec. 17 New England Journal of Medicine. But the results of clinical trials of the Pfizer-BioNTech and Moderna vaccines suggest that protection begins two weeks after the first dose: the Pfizer-BioNTech vaccine was 50 percent effective after the first dose and the Moderna had about 80 percent of effectiveness (SN: 18/12/20). It is unknown how long that protection may be, says Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago, but it would be strange to see it disappear quickly.
Cobey is one of the scientists who is not worried about the risk of a long delay between shots. Instead, expanding how many people receive the first dose could help control how much the coronavirus changes, she says. It is said that even the partial protection that people can get from a single dose "will certainly decrease the prevalence of infection." Fewer infections in general would mean fewer coronavirus variants in general circulating among people. By virtue of the figures, it is possible that the coronavirus may not accumulate as many mutations that may help bypass the immune systems.
And even if a virus accumulates mutations that help it dodge the immune response as a result of dose delay, these changes can in turn damage essential viral functions such as bursting in and hijacking a host cell. A virus that can escape immunity, for example, may end up being less transmissible. For now, it is unclear what may happen to the coronavirus, which generally mutates more slowly than other similar viruses thanks to a single correction enzyme that acts as a spelling checker for the letters that make up the coronavirus genetic plan (SN: 1/28 / 20).
What’s more, the immune responses a person produces also don’t attack just one part of a virus. Antibodies, for example, including those induced by vaccines, strike many different parts of viral proteins, making it difficult for the virus to escape. And over time antibodies can improve in their work (SN: 11/24/20). Therefore, most mutations are unlikely to cause antibodies to be completely ineffective.
“It all comes together and it’s a fairly high barrier” for the virus to evolve, says Adam Lauring, an infectious disease physician and virologist at the University of Michigan School of Medicine in Ann Arbor.
In laboratory experiments, for example, the serum of the COVID-19 patient that harbors countless antibodies against coronavirus still prevents the coronavirus from infecting cells in a dish, even if there are viral mutations, the researchers reported in a preliminary study published on 4 January at bioRxiv.org. Although some mutations, including one present in a coronavirus variant now circulating in South Africa, have made antibodies in serum less effective in preventing viruses from infecting cells, the serum virus stopping activity has not permanently disappeared.
Still, this does not mean that a potentially risky viral evolution does not occur as a result of delayed doses. “I think this is something we should study and we should look at for sure,” Lauring says. For now, "I'm not sure we know enough to say with confidence what one strategy or another (vaccine dosage) is going to do."
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