Visitors are queuing up to get an injection of a COVID-19 vaccine at a national health service center in Birmingham, UK. Due to scarce vaccination, the UK has extended the interval between doses.
Jacob King / PA Wire / Bloomberg via Getty Images
By Meredith Wadman
Science‘COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
Paul Bieniasz did not invent words in a sarcastic New Year’s statement he tweeted. If he wanted to create a new, vaccine-resistant version of the pandemic coronavirus, the Rockefeller University virologist wrote: ‘After developing a remarkable two-dose vaccine, [I’d ]… CONTROL IT WITH MILLIONS OF PEOPLE – BUT SUSPEND THE SECOND DOSE. … If we let the immunity go down for a while, we say 4 to 12 weeks, we can just hit the sweat spot ‘- and create a virus that can thwart the vaccine.
Bieniasz responded to the UK’s decision on December 30 to allow up to 12 weeks between doses of two authorized vaccines, rather than the three or four weeks tested in the clinical trials of the vaccines. The British vaccine experts were desperate to tame a huge increase in cases and worried about the spread of a new, more contagious variant of the virus, aiming to quickly put at least some protection in the arms of so many people if possible.
Related
In a similar tactic to stretch scarce vaccine supplies, Russia on Monday revealed that it would test its two-dose Sputnik V vaccine to see if only one dose – “Sputnik Light” – would be effective. And yesterday, the Trump administration announced that it would no longer withhold 50% of the available vaccine supply in the United States to ensure timely second doses.
But Bieniasz and other virologists are concerned that prolonging the dosing interval could result in millions of people with only partial immunity if they wait for their second dose – a possible breeding ground for vaccine-resistant mutations. “If we end up getting just one dose without doses available for a timely boost, that would be a problem in my opinion,” says Florian Krammer, a virologist at the Icahn School of Medicine on Mount Sinai.
However, experts do not agree on the high risk of long-term dose delay, especially when weighed in many places against the current spread of the pandemic coronavirus, SARS-CoV-2. “It’s a massacre out there,” said Andrew Read, an evolutionary microbiologist at Pennsylvania State University. “Half of them should be twice as many people with partial immunity as full immunity.”
But the record numbers also create an extraordinary environment – with countless billions of viral replications occurring every second – for mutations if the virus makes mistakes in copying its genetic alphabet. One viral variant, first observed in South Africa, has developed two mutations that block the effectiveness of antibodies used in the treatment of COVID-19, which has led to the specter that it also contains antibodies through vaccines. can block.
One of these mutations has reduced the ability of antibodies in some recovered COVID-19 patients ten times or more to neutralize viruses that express the coronavirus ear protein, according to a recent preview by Jesse Bloom and Allison Greaney of the Fred Hutchinson Cancer Research Center and their colleagues.
Virologists are concerned that prolonging the dose interval of, for example, 3 weeks to 3 months can accelerate the emergence of such mutants by creating a pool of sub-immune people who have enough antibodies to slow down the virus and prevent symptoms. , but not enough to erase it. out. These people can incubate viruses with mutations that allow them to evade antibody-induced antibodies – for example, by altering the amino acid sequence at a site where antibodies were previously bound, preventing the virus from entering and repeating cells. Because most COVID-19 vaccines generate immunity to only one protein, the field protein on the surface of the virus, the new vaccines may be easier to evade mutant viruses than other vaccines that elicit broader immunity.
Some data support the possibility that partial immunity may cause new variants. For example, a case study recently conducted in The New England Journal of Medicine reported how, in a prolonged, ultimately fatal case of SARS-CoV-2 in an immunocompromised man, the virus mutated rapidly compared to the virus that was spreading in the general population.
But evolutionary biologists who use computer modeling to generate viral ‘escape’ scenarios of vaccines say there is not enough data yet to calculate this still hypothetical risk, and that any mutation is unlikely to lower the vaccine’s effectiveness. . Bloom notes that “even [the] worst mutations ”seen so far have only partially eroded the efficacy of antibodies from recovered patients’ blood.
‘Most people I know do dynamic modeling in public health and evolution [vaccine escape] is a secondary … concern. That it is more important to immunize broadly just now. I’m in that camp, ”said Sarah Cobey, an epidemiologist and evolutionary biologist at the University of Chicago.
Historically, few viruses have succeeded in developing vaccine resistance, with the notable exception of seasonal flu, which develops so rapidly on its own – without vaccination of the vaccine – that it requires a newly designed vaccine annually. The poliovirus mutates faster than the new coronavirus, but polio vaccines remain highly effective. And the measles virus mutates about twice every million times it repeats itself, according to a pre-print published in October 2020. But in 57 years, the measles virus could not end up in the highly effective vaccine, made from live, attenuated virus, in part because the vaccine elicits such a wide range of antibodies that no single mutation has a major impact.
If the new coronavirus significantly mutates over time, researchers could update the vaccines, says Lucy Van Dorp, a computational geneticist at University College London. She notes that the mRNA vaccines made by Pfizer and Moderna are “very suitable for updates.” The CEO of BioNTech, which developed the first vaccine from Pfizer, recently said The Financial Times “We can make a new vaccine in 6 weeks.”
Yet scientists want to solve their theoretical debate with data. Laboratory studies investigate how well antibodies from vaccinated people neutralize the different strains of the virus. And the data soon expected from late-stage vaccination trials in South Africa, which began before the new strain appeared in the country, should shed light on the strain’s ability to escape from these vaccines.
Meanwhile, a live experiment in the UK is underway to extend the dose range. Bieniasz says he cannot say with certainty whether the virus strains will result in vaccines. “But if that was my goal, I would do it.”