Britain opts for mix-and-match vaccinations, confounding experts
By Katherine J. Wu
Amid a sputtering vaccine rollout and fears of a new and potentially more transmissible variant of the coronavirus, Britain has quietly updated its vaccination playbook to allow for a mix-and-match vaccine regimen. If a second dose of the vaccine a patient originally received isn’t available, or if the manufacturer of the first shot isn’t known, another vaccine may be substituted, health officials said.
The new guidance contradicts guidelines in the United States, where the Centers for Disease Control and Prevention has noted that the authorized COVID-19 vaccines “are not interchangeable,” and that “the safety and efficacy of a mixed-product series have not been evaluated. Both doses of the series should be completed with the same product.”
Some scientists say Britain is gambling with its new guidance. “There are no data on this idea whatsoever,” said John Moore, a vaccine expert at Cornell University. Officials in Britain “seem to have abandoned science completely now and are just trying to guess their way out of a mess.”
Health officials in Britain are caught in a deadly race with the virus, which is surging again, and are struggling to get as many people vaccinated as possible. Hospitals continue to strain under a crush of coronavirus patients, and tens of thousands of new infections are reported each day. Schools in London and other regions hit hard by the virus will remain closed for at least the next two weeks, government officials said Friday.
The country has issued an emergency green light to two vaccines, developed by Pfizer and AstraZeneca. According to Britain’s new guidance, “every effort should be made” to complete a dosing regimen with the same shot first used. But when “the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product” the second time around.
“This option is preferred if the individual is likely to be at immediate high risk or is considered unlikely to attend again,” the recommendation said. Because both vaccines target the spike protein of the coronavirus, “it is likely the second dose will help to boost the response to the first dose.”
Following requests for comment, officials at Public Health England drew attention to the similarities between the Pfizer and AstraZeneca vaccines, and said that clinical trials testing mixed regimens were to start sometime this year.
It is far from certain that the vaccines are interchangeable, several researchers said.
“None of this is being data driven right now,” said Dr. Phyllis Tien, an infectious disease physician at the University of California, San Francisco. “We’re kind of in this Wild West.”
Steven Danehy, a spokesman for Pfizer, pointed to the company’s late-stage clinical trial findings, which relied on a two-dose schedule of its vaccine that was 95% effective at preventing COVID-19.
“While decisions on alternative dosing regimens reside with health authorities, Pfizer believes it is critical health authorities conduct surveillance efforts on any alternative schedules implemented and to ensure each recipient is afforded the maximum possible protection, which means immunization with two doses of the vaccine,” Danehy said.
Both Pfizer’s and AstraZeneca’s vaccines introduce into the body a protein called spike that, while not infectious itself, can teach immune cells to recognize and fight off the actual coronavirus.
But the vaccines impart their immunological lessons through different methods, and do not contain equivalent ingredients. While Pfizer’s vaccine relies on a molecule called messenger RNA, or mRNA, packaged into greasy bubbles, AstraZeneca’s shots are designed around a virus shell that delivers DNA, a cousin of mRNA.
Both vaccines are intended to be doled out in two-shot regimens, delivered three or four weeks apart. While the first shots of each vaccine are thought to be somewhat effective at preventing COVID-19, it’s the second dose — intended as a sort of molecular review session for the immune system — that clinches the protective process.
While it’s possible that swapping out one vaccine for another may still school the body to recognize the coronavirus, it is a scientific gamble. With different ingredients in each vaccine, it’s possible people will not benefit as much from a second shot. Mixing and matching could also make it more difficult to collect clear data on vaccine safety.
Without evidence to back it, the hybrid vaccination approach seems “premature,” said Saad Omer, a vaccine expert at Yale University. Still, it’s not without precedent: Health authorities like the CDC have previously said that if it’s impossible to give doses of a vaccine from the same manufacturer, “providers should administer the vaccine that they have available” to complete an injection schedule.
In a controversial move, the British government this week also decided to front-load its vaccine rollout, delivering as many first doses to people as possible — a move that could delay second shots up to 12 weeks.
The speedy deployment might afford more people partial protection against the virus in the short term. But some experts, including Moore, worry that this, too, might be unwise, and could imperil vulnerable populations.
A vaccination gap that stretches on too long may hamstring the second shot’s ability to boost the protective powers of the first — or raise the odds that people will forget, or decide against, returning for another injection.
The whiplash changes in guidance in Britain, many made without public meetings or strong data, may erode trust in vaccination campaigns and public health measures in general, Tien said.
“We’re making an assumption that the public is just going to listen and come in and get the vaccine,” she said. “I’m worried that’s not going to happen.”