麻豆传媒

As Great Britain continues to stretch out the interval between the first and second doses of the COVID-19 vaccine to 12 weeks, data out Wednesday seem to support doing so -- but concerns remain.

Physicians and public health experts have questioned whether the national strategy of getting as many first doses into arms as quickly as possible -- by extending the time between first and second doses -- is medically and ethically sound. A new study of the AstraZeneca/Oxford vaccine has helped ease the debate, though not entirely.

The study, , showed that the AstraZeneca/Oxford vaccine during the 12-week interval between first and second doses, the Britain's Department of Health and Social Care announced Wednesday.

However, clinical trials used to authorize the Pfizer/BioNTech and Moderna vaccines didn't examine whether such a lag between first and second doses would have an impact on efficacy.

The Pfizer/BioNTech vaccine was the first authorized for use in the U.K., in early December. Weeks later, British authorities moved to extend the time between first and second doses to 12 weeks -- just after the country identified the novel, more transmissible B.1.1.7 variant that was circulating there. The country's Joint Committee on Vaccination and Immunization supported government officials' decision to delay doses in light of the new variant.

It's a strategy that has continued as the AstraZeneca/Oxford vaccine and the Moderna vaccine were authorized for use in the country.

Initially, the strategy to extend the dosing interval included doing so for individuals who had already consented to and received the first dose of the Pfizer/BioNTech vaccine with the information they would get a second shot 3 weeks later, Helen Salisbury, a general practitioner and honorary senior clinical lecturer at the University of Oxford, told 麻豆传媒. "That's what we have the data for," she said of the 3-week interval for the Pfizer/BioNTech vaccine.

One of the initial concerns from the physician community surrounded changing the process from what individuals had consented to, and exacerbating a lack of trust some people already hold about vaccines more broadly, Salisbury said.

But the situation has evolved.

The AstraZeneca/Oxford vaccine had another set of timelines built into trialing it, looking at longer gaps between first and second shots, Salisbury noted. And, now, individuals receiving first doses of other vaccines are doing so with the understanding that their second dose will be given 12 weeks later.

If "our best guess" is that the pandemic will end sooner by spacing out doses -- helping to address shortages and vaccinating more people at 76% efficacy rather than fewer people with slightly better protection -- that's likely the right thing to do, Salisbury said. "So far, the data is looking relatively good."

Siu Ping Lam, PhD, director of licensing at Britain's Medicines and Healthcare products Regulatory Agency, also pointed to the latest AstraZeneca/Oxford data.

"The data presented in this pre-print are very reassuring and are consistent with those seen at the time of the approval," he said in a statement provided to 麻豆传媒. "This data has been submitted to us and, subject to our review, provides further robust evidence to support a 12-week dosing interval for COVID-19 vaccine AstraZeneca. It also shows that, from day 22 to day 90, the first dose of the vaccine has good protection against COVID-19."

However, the U.S. isn't rushing to follow suit.

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, addressed the U.K.'s strategy of delaying doses during Wednesday's White House COVID-19 Response Team briefing.

"We have heard from studies emanating out of the AstraZeneca platform, that in the U.K. they're talking about the possibility -- since their data seems to show this -- that if you prolong the interval between the first and second dose -- in fact even go with a single dose -- you can get good results," Fauci said during the briefing. "And in fact, the interval between the first and second dose can now be measured in months, according to their own data, and that is actually a favorable response."

"We certainly respect that the U.K. scientists and health officials are going by their data, and letting their own data for their own platform dictate their policy," he continued. "The question is asked often, 'then why don't we do the same thing with our candidates that are now being distributed to people in the United States?' And the response is simple. We also are going very much by the data and the science that has emanated out of very large clinical trials. The Moderna trial -- with 30,000 people -- and the Pfizer trial -- with 44,000 people -- indicate to us that maximum responses are given with a prime followed by a boost within 21 days with Pfizer and 28 days with Moderna."

For people who are unable to get the second dose of the vaccine within those time frames due to special circumstances, the CDC has said that it is okay to receive the boost within four to weeks, Fauci said during the briefing. But that doesn't mean that is the desired dosing schedule.

"We feel strongly that we will go by the science, which has dictated for us the optimal way to get the 94% to 95% response," he added.

Arthur Caplan, PhD, professor of bioethics at NYU Grossman School of Medicine, has also emphasized adhering to available data.

There are questions about guaranteeing there will be enough vaccine for second doses if they are delayed, determining how long protection from the first dose might last, and how new variants change what is known about first doses, Caplan told 麻豆传媒. He added that one dose may give people a false sense of security -- they may stop masking and social distancing, and that could bring its own challenges.

Veering from available data could have other consequences as well.

Once officials start changing what was promised, that can lead to mistrust, Caplan said.

"It's a version of an experiment," he said of changing vaccine dosing from what was tested in the registration trials. "You have to really treat that, in my mind, as an experiment and get people's informed consent."

There are a lot of ideas about how to vaccinate and protect as many people as possible, Caplan said, including having individuals get a first dose of one vaccine and a second dose of another. But again, he added, it's an experiment. And more vaccines are expected to come online in the coming months.

Salisbury in the U.K. also noted that there are questions that remain, such as whether frontline hospital staff at high risk of occupational exposure should be given both doses within a shorter timeframe than 12 weeks. Additionally, there is limited data on the vaccination of adults ages 80 and up.

As for how variants may contribute to the debate about delayed doses, Salisbury said that it depends on whether many partially vaccinated people end up with mild infections, providing the virus the opportunity to mutate. However, one argument is that more people vaccinated with first doses will contribute to fewer people infected, thwarting the ability of the virus to mutate. "It's a numbers game," she said.

As of Wednesday, CDC data indicated that had received at least one dose of a COVID-19 vaccine, of whom 6.4 million had gotten both doses. Only the Pfizer/BioNTech and Moderna vaccines are available in the U.S.; AstraZeneca's U.S. trial was halted for 7 weeks last fall. Between that and a , FDA authorization is not expected until April.

Comment