A new British study reports that mixing doses of the Pfizer-BioNTech and AstraZeneca-Oxford vaccines generates an immune response stronger than two rounds of an AstraZeneca dose, although the highest antibody response was seen in people fully vaccinated with Pfizer.
The early results, which have not yet been reviewed, have been published as a paper Posted online by Lancet on Monday.
The results come from the University of Oxford led by Com-COV . study, which explores the use of different combinations of approved COVID-19 vaccines.
This round of research looked at several vaccine combinations: two doses of Pfizer, two doses of AstraZeneca, and mixing doses with AstraZeneca or Pfizer as the first injection and one for the second dose.
“The mixed schedules generated an immune response that was higher than the limit set.” [AstraZeneca] “A vaccine we know is very effective against severe disease,” said study lead author Dr Matthew Snape, associate professor of pediatrics and vaccines at Oxford University, during an interview with CBC News.
Both combination schedules produced stronger responses from two doses of AstraZeneca, but the research team observed the highest antibody response in people who received two doses of the Pfizer vaccine.
“Whether that translates into better protection or longer duration will have to see,” Snape said.
The team found that the AstraZeneca shot followed by Pfizer produced the best T-cell responses, as well as a higher antibody response than Pfizer followed by AstraZeneca.
The results were for two doses of different vaccine combinations, given every four weeks to 830 people, in a blind, non-inferior participant trial — the type of study used to prove that an experimental treatment is not much worse than an active treatment. The treatment it is being compared to.
Snape said he was surprised to discover that the order of the vaccines used in the mixed schedules seemed to matter “a lot.”
He continued, “AstraZeneca followed by Pfizer produced slightly higher levels of antibodies than Pfizer followed by AstraZeneca. And that’s interesting.”
“And that, I think, opens the door for further research to find out why that is.”
Watch | Canada agrees to mix COVID-19 vaccines:
The National Immunization Advisory Committee says the AstraZeneca-Oxford COVID-19 vaccines can be replaced with Pfizer or Moderna for the second dose. Limited evidence suggests that immunity from mixing doses is equally good, and may be better than two of the same doses. 2:00
Results ‘supportive’ of Canadian directive
The findings provide early evidence that a mixed dosing schedule can be a smart approach in certain situations, providing some support for Canada’s unconventional move to Allowing different approved vaccines to be used interchangeably in certain cases.
The advisory board’s decision was prompted by concerns about the supply — and reports of rare but serious blood clots following the AstraZeneca vaccination — which has since led to Canadians across the country exchanging shots of AstraZeneca, Pfizer and Moderna 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 provides the largest look yet at mixed dosing schedules and supported some of his findings on a smaller scale.
“I think all of that will give us more confidence in mixing our vaccines,” he continued.
Watch | The NACI recommends against using AstraZeneca:
The National Immunization Advisory Committee (NACI) recommends that provinces stop giving AstraZeneca in most cases — even as a booster dose to people who have already received their first doses of the product. The committee cites better immune responses with mRNA vaccines and increased supply as reasons for the new guidelines. 1:59
This reassurance may be even more important for Canadians who took AstraZeneca as their first dose but found themselves torn about the next option, notes immunologist Don Bowdish, a professor at McMaster University in Hamilton.
“They can now rest assured that if they choose to acquire AstraZeneca, they will be protected,” she said. “And if they choose to get the mRNA vaccine, they will also be protected.”
Infectious disease specialist and associate professor at the University of Saskatchewan Dr. Alexander Wong, who also reviewed the research, said the hopeful findings suggest Canadians should not have “currently concerns about any of these groups.”
“The bottom line is that it’s supportive of the guidelines that have been provided so far, so anyone who’s had a first dose of AstraZeneca and a second dose of the mRNA vaccine — great job,” he said.
Switching up different doses isn’t a “magic combination” to generate a stronger immune response, Snape says, given that doubling down on Pfizer came out on top, but he stressed that all of the options studied generated protective responses.
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What is missing from this British research is extensive and long-term safety data.
This means that this research cannot detect any potential warning signs that may arise from mixing forms of vaccine technology, which have been individually linked to some health problems.
There have been reports of heart inflammation in rare cases after mRNA vaccines, for example, and a blood clotting condition associated with AstraZeneca vaccine-induced thrombocytopenia, or VITT.
Pfizer and Moderna’s shots use mRNA technology, while the AstraZeneca vaccine is a vector-based viral option.
“Studies like ours generate useful start-up data about immune responses and short-term reactions, but they really don’t replace active safety monitoring as the vaccine is being rolled out,” Snape said.
Virologist Alison Kelvin, with the University of Saskatchewan Vaccines and Infectious Diseases Organization, agrees that Canada will need to continue monitoring for Adverse Reactions for all dosing schedules, including mixed brands.
She also stressed that more research is needed to fully understand the impact of swapping other vaccines.
“Although we really understand that the mRNA platforms are quite similar between Pfizer and Moderna, it was good to see mixing those vaccines for solid evidence,” she said.
Snape’s team will continue its research in the coming months, with more studies looking at longer time frames between doses and mixed schedules showing other vaccines such as Moderna and the Novovax vaccine not yet approved for use in Canada.
The latest study also builds on his team Previous results of mixing doses, which found that interchangeability in different brands could increase the chance of someone having mild or moderate reactions such as fatigue, headache or fever — signs that, at the time, experts said indicated potential success in building a strong immune response.
Snape stressed that while the latest findings could be used to give flexibility in rolling out the vaccine, including to Canada, the study was not large enough to recommend a broader shift away from clinically approved schedules on its own.
“I’ve had an experience in Canada, where you’re actually doing this schedule almost before the evidence,” he said.
“But what we have now is reassuring.”
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