Mixing Pfizer, AstraZeneca doses provides strong immune response against COVID-19: study

Mixing doses of the Pfizer-BioNTech and AstraZeneca-Oxford vaccines generate a stronger immune response than having two rounds of the AstraZeneca shot, new U.K. research suggests, though the highest antibody response was seen in people being fully vaccinated with Pfizer.

The early findings, which haven’t yet been peer-reviewed, were released as a paper published online by the Lancet on Monday. 

The results come from the University of Oxford-led Com-COV study, which is exploring the use of different combinations of approved COVID-19 vaccines.

This round of research looked at several vaccine combinations: two doses of Pfizer, two of AstraZeneca, and mixing doses with either AstraZeneca or Pfizer as the first shot and the other for the second.

“The mixed schedules did generate an immune response that was above the threshold set by the [AstraZeneca] vaccine, which we know is very effective against severe disease,” said the study’s chief investigator, Dr. Matthew Snape, an associate professor in pediatrics and vaccinology at the University of Oxford, during an interview with CBC News.

Both mixed schedules produced stronger responses than two doses of AstraZeneca, but the research team observed the highest antibody response in people receiving two doses of the Pfizer vaccine.

“Whether that translates into better protection or longer duration, we will have to see,” Snape said.

An AstraZeneca shot followed by Pfizer produced the best T-cell responses, the team found, and also a higher antibody response than Pfizer followed by AstraZeneca.

The results were for two doses of different vaccine combinations, given at four-week intervals to 830 people, in a participant-blind, non-inferiority trial — a type of study used to demonstrate that an experimental treatment is not substantially worse than an active treatment it’s being compared to.

Snape said he was surprised by the finding that the order of vaccines being used in the mixed schedules seemed to matter “quite a lot.”

“AstraZeneca followed by Pfizer generated antibody levels that were quite a bit higher than Pfizer followed by AstraZeneca. So that is intriguing,” he continued. 

“And that does, I think, open the door for more research to work out why that would be.”

WATCH | Canada OKs mixing COVID-19 vaccines:

The National Advisory Committee on Immunization says AstraZeneca-Oxford COVID-19 vaccines can be swapped for Pfizer or Moderna for the second dose. Limited evidence suggests the immunity from mixing doses is just as good, and may be better than two of the same. 2:00

Findings ‘supportive’ of Canadian guidance

The findings offer early evidence that a mixed dosing schedule could be a savvy approach in certain situations, offering some support for Canada’s unorthodox move to allow various approved vaccines to be used interchangeably in certain situations.

It was an advisory body decision prompted by supply concerns — and reports of rare, but serious, blood clots following AstraZeneca vaccinations — which has since led to Canadians across the country swapping between AstraZeneca, Pfizer and Moderna shots in recent weeks.

Christopher Richardson, a professor in the department of microbiology and immunology at Dalhousie University in Halifax, praised the new preprint study for its scope, saying it offers the largest look yet at mixed dosing schedules and backed up some of his own smaller-scale findings.

“I think it will all supply more confidence in us mixing our vaccines,” he continued.

WATCH | NACI recommends against AstraZeneca:

The National Advisory Committee on Immunization (NACI) is recommending the provinces stop administering the AstraZeneca vaccine in most cases — even as booster shots for people who’ve already received first doses of the product. The committee is citing better immune responses by mRNA vaccines and greater supply as reasons for the new guidelines. 1:59

That reassurance could matter most for Canadians who had AstraZeneca’s shot as a first dose but found themselves torn on what option to get next, noted immunologist Dawn Bowdish, a professor at McMaster University in Hamilton.

“They can now rest assured that if they choose to get AstraZeneca, they’ll be protected,” she said. “And should they choose to get an mRNA vaccine, they’re also going to be protected.”

Infectious disease specialist and University of Saskatchewan associate professor Dr. Alexander Wong, who also reviewed the research, said the hopeful findings suggest Canadians should have “no concerns at this point in time about any of these combinations.”

“Bottom line is it’s supportive of the guidance that’s been provided thus far, so anybody who’s had a first dose of AstraZeneca and a second dose of an mRNA vaccine — great job,” he said.

Snape says swapping in different doses isn’t a “magic combination” for generating a stronger immune response, since doubling up on Pfizer came out on top, but he stressed that all the options studied generated protective responses. 

Broader safety data needed

What’s lacking in this U.K. research is large-scale, long-term safety data.

That means this research couldn’t catch any possible warning signs that may arise from mixing forms of vaccine technology, which have individually been linked to certain health problems.

There have been reports of heart inflammation in rare cases following mRNA vaccinations, for instance, and the blood-clotting condition tied to the AstraZeneca shot which has been dubbed vaccine-induced immune thrombotic thrombocytopenia, or VITT.

Both Pfizer and Moderna’s shots use mRNA technology, while AstraZeneca’s vaccine is a viral vector-based option.

“Studies such as ours generate useful starting data on immune responses, and short-term reactions, but they really aren’t taking the place of active safety surveillance as the vaccine is being rolled out,” Snape said.

Snape’s team will be continuing its research in the months ahead, with further studies looking at longer time frames between doses and mixed schedules featuring other vaccines such as the Moderna shot, and the Novovax vaccine which is not yet approved for use in Canada.

The latest study also builds off his team’s earlier results on mixing doses, which found swapping in different brands could hike the chance of someone having mild or moderate reactions like fatigue, headache or a fever — signs which, at the time, experts said pointed to potential success in building a strong immune response. 

Snape stressed that while the latest findings could be used to give flexibility to vaccine rollouts, including Canada’s, the study wasn’t large enough to recommend a broader shift away from clinically approved schedules on its own.

“You’ve had an experience in Canada, where you are actually implementing this schedule almost ahead of the evidence,” he said. 

“But what we have is now reassuring.”

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