IIn an extraordinary time, British health authorities are taking extraordinary measures to repel Covid-19. But some experts believe that they are also taking a serious gamble.
In recent days, the British have said they will extend the interval between the administration of the two doses required for Covid-19 vaccines already in use – possibly to three months, instead of the recommended three or four weeks. And they said they may allow the first dose and second dose for one person from different vaccine manufacturers if the corresponding vaccine is not available.
There is a desire to vaccinate as many people as quickly as possible, especially with Britain facing high levels of transmission of a seemingly contagious form of SARS-CoV-2, the virus that causes Covid-19.
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But they also effectively make the country a living laboratory. The moves are based on small pieces of evidence extracted from “substructures of substructures” of participants in clinical trials, as one expert describes it for STAT, and on general principles of vaccination, rather than on actual research on the specific vaccinations used . If the efforts succeed, the world will have learned a lot. If they fail, the world will also have gained important information, although some fear it could be very costly.
U.S. health officials have ruled out the possibility that the U.S. would follow Britain’s lead, with Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, saying the vaccines used – one by Moderna, the other by the Pfizer and BioNTech Partnership – will be deployed here using the schedules which was tested in phase 3 trials that generated the evidence on which the Food and Drug Administration approved the vaccines for emergency use.
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Although data from both indicate that the vaccines start to protect about 10 or 12 days after the first dose, it is not known how long the initial protection lasts. In clinical trials, the levels of neutralizing antibodies, which are thought to play a critical role in protection against infection, were not significant after the first dose of vaccine for the Pfizer vaccine.
‘Although we think a single shot can provide protection for more than four weeks, we just do not know. We do not know when it will decrease, ”says John Mascola, director of the NIAID’s center for vaccine research. Mascola said Operation Warp Speed, the federal government’s project to detect Covid vaccines, ruled out the possibility of changing vaccination schedules before Britain decided to do so.
Paul Bieniasz of Rockefeller University is one of those who is watching the developing situation in Britain with horror. A retrovirologist working on HIV research on SARS-2, Bieniasz is studying how the virus gets mutations that make it possible to evade the protective antibodies that humans develop when they contract Covid-19, or when vaccinated against it .
Bieniasz believes that Britain is repeating the experiments it did in its laboratory in humans and could possibly promote the form of a vaccine-resistant virus.
On New Year’s Day he posted a short, sarcastic dissertation – ‘Musings of anonymous, piss off virologist’ – on Twitter outlining how one can go about making Covid vaccines ‘powerless’ if that’s anyone’s goal. He suggested that millions of people who are at risk of contracting the disease on a daily basis provide incomplete protection by delaying the second dose of vaccination.
“My concern as a virologist is that if you want to make a vaccine-resistant strain, you have to build up a group of partially immunized individuals in the teeth of a very common viral infection,” Bieniasz told STAT. Even not rolling out the vaccine at all when there is so much transmission is far from ideal, he said, suggesting that it would have been safer to beat the amount of virus that was in circulation before using the vaccination of the vaccine is started.
‘You’re actually taking the opportunity for the virus to learn more about the human immune system. Read more about antibodies. Learn how to dodge it, ”he said.
Isabella Eckerle, a coronavirus researcher at the Geneva Center for Emerging Viral Diseases, shares Bieniasz’s concern that Britain is increasing the potential for so-called escape mutants. She understands the need for public health behind his approach, but is concerned about a large number of people being partially protected for several months. Britain first vaccinates its oldest citizens. The immune system of the elderly does not function as well as that of younger adults; some will inevitably catch Covid while waiting for their second dose of vaccine, she said.
Reports from people who have been partially vaccinated and who are getting Covid can also inherit confidence in the vaccines, Eckerle said: harm done, I think. ‘
Stephen Goldstein, a virologist at the University of Utah who specializes in coronaviruses, said that using Britain’s approach during a limited amount of vaccine could cause other problems.
‘If we all get one dose of vaccination and … six weeks later, the effectiveness is now about 30% and at that point we do not have the doses to increase it, because we are using up their second doses in another round of first doses has. “It could be a disaster,” he said.
Not everyone agrees that there is a disaster. Some think it makes sense, given the increase in Britain in cases and the rapid spread of the B.1.1.7 variant, which according to studies is 50% more transmissible than the viruses that replace it quickly.
“At the core of my being, I really wish we could stick to the original vaccine schedule, because that’s the safest thing to do,” said Akiko Iwasaki, a virologist and immunologist at Yale University. her support for the British approach. “But when I see what’s going on in the world and just look at the situation of poor implementation and distribution, I feel frustrated that we have to come up with some other options.”
(Iwasaki, however, was upset to see Britain’s instructions to clinicians that they could use a second dose of mismatched vaccine if it was the only option that would not be done in the context of a clinical trial. Although there is reason to believe that enhancement with a different type of vaccine may in some cases actually be useful – especially if the first dose is a vaccine such as the AstraZeneca vaccine that uses a harmless virus that fuses SARS-2 genetic material is – has the approach not been used at all studied in clinical trials.
“They waste the chance if they just do it randomly and not even follow up on the effectiveness of the combination,” Iwasaki said. “So yes, I feel much more comfortable if it was an experiment.”)
Rajeev Venkayya, president of global vaccinations for Takeda Pharmaceuticals, also believes Britain’s decision to extend the vaccine interval is “justifiable.”
‘Of course we all want to see vaccines used exactly as they were tested in phase 3 efficacy trials. I think there is no debate about that. The question is: Do you have evidence to support flexibility? And here I do think – and this is specifically for the AstraZeneca vaccine – it appears that there is additional evidence that could support a modified recommendation, ”said Venkayya, who served as special assistant to President George W. Bush and senior director has. for bio defense. In the role, Venkayya was the person in the White House for the pandemic preparatory efforts caused by the spread of H5N1 bird flu.
While the US trial of the AstraZeneca vaccine tested two doses given four weeks apart, studies conducted by the company elsewhere gave two participants the doses at intervals of six to eight weeks, or nine to 11 weeks, and some received the doses at an interval longer than 12 weeks.
The Pfizer and Moderna vaccines are the first to use mRNA technology, and the companies have not studied the extensive dosing schedules. Pfizer objected to the suggestion that the vaccine should be used at longer intervals.
Venkayya, whose thinking is influenced by his years in the White House, said that sometimes policies have to be done without perfect data.
“I think that to take the standards we usually apply to the amount of evidence we need before we make decisions and recommendations on vaccine use, it needs to change in the midst of a crisis like this,” he said. . ‘I think there’s the way we do medicine and public health in peacetime … where we have the luxury of taking the time and effort to gather enough data to come to a conclusion . You just do not have that luxury in the midst of a crisis. ”