Vaccine mixing appears safe: study
Adds ‘flexibility and resilience’ to rollout
People who receive one dose each of Astrazeneca and Pfizer COVID-19 vaccines are more likely to feel a bit unwell for a day or so than if they had both doses from the same vaccine, according to early results from a much-anticipated trial.
But any side effects were short-lived and there were no other safety concerns.
At a minimum, the preliminary data suggest mixing Astrazeneca and Pfizer-biontech appears safe, even though people are more likely to experience chills, fatigue, headache, feverishness, joint pain, malaise and muscle aches than the “nonmixed” group.
The mix-and-match trial led by University of Oxford researchers is being watched by health authorities the world over, including Canada. The results, already shared with Canada’s expert panel of vaccine advisers, could make vaccination campaigns more nimble and ease nerves rattled over the risk of remote but serious blood clots linked to Astrazeneca.
Several provinces are now mulling using Pfizer or Moderna as a second dose for those who received Astrazeneca for their first.
However, the researchers said they did not see a clear signal of an increased risk of vaccine-induced thrombotic thrombocytopenia (VITT) on a second dose of Astrazeneca.
That would seem to support sticking with AZ for the second dose.
“But, of course, it’s up to every country and their own experience as to what they think will be the best use of these vaccines,” said chief investigator Dr. Matthew Snape, an associate professor in pediatrics and vaccinology at Oxford.
Pfizer and Moderna, both MRNA vaccines, differ from Astrazeneca. They use different approaches. And, until now, there was no data on what happens when you mix them. What happens when a person is primed with one type of vaccine, and then boosted with another?
In a peer-reviewed letter published Wednesday in the Lancet, researchers reported greater “systemic reactogenicity” — or side effects — in the mixed doses group.
In all, 830 people aged 50 and older, including those with mild to moderate underlying health problems, were assigned at random to receive one of four different vaccine combinations: a first dose of Astrazeneca, followed by either Pfizer or a second dose of Astra Zeneca; or a first dose of Pfizer, followed by either Astrazeneca or a further shot of Pfizer. People were given vaccines at four- or 12-week dosing intervals.
The driver behind this study was to look at a way of building “flexibility and resilience into the vaccine rollout” in the event of supply problems, Snape said.
People reported stronger reactions to the first dose of Astrazeneca than the first dose of Pfizer, but the second dose of Pfizer produced more side effects than the first. The Pfizer vaccine was also more painful, according to the volunteers’ symptom diaries.
But, in what Snape called a “really intriguing finding,” both mixed schedules caused more side effects than the non-mixed doses. After the second dose of Astrazeneca, around 10 per cent of participants reported chills. But if AZ was followed by Pfizer, that increased to 40 per cent. If it was Pfizer followed by Pfizer about 25 per cent had chills; Pfizer followed by Astrazeneca increased it to 45 per cent.
Similar increases were observed for feeling feverishness, headache, fatigue and muscle aches. Participants didn’t know what vaccines they were getting, and still don’t.
It’s not clear why mixing doses increased the frequency of reactions, or whether or not it has led to a better immune response. Those data are due in June.
“We know that at an individual level that doesn’t always apply,” Snape said. “You’d like to think that if you had a really strong vaccine reaction that means you have a better immune response. That correlation isn’t as robust as you might expect.”
Volunteers were asked to report symptoms for a week after the second booster dose. No VITT, the blood-clotting disorder linked to Astrazeneca, was found in any group at day seven, post-boost, the researchers reported.
Most people overall didn’t experience any reactions, regardless of what combination they received. And of those who did, most were mild. Symptoms dropped off after two or three days, and no one was hospitalized.
“But one of the things it’s telling us is that you wouldn’t want to immunize a ward full of nurses on the same day with a mixed schedule, because you may have high rates of absenteeism the same day,” Snape said.
The data are based on people given shots four weeks apart. Researchers are also testing a 12-week interval, and have begun adding Moderna and Novavax vaccines into the mix. They’re also looking at whether routine doses of acetaminophen might make mixed doses better tolerated.
The trial involved people aged 50 and above, and reactions might be higher still in younger age groups.
“We have actually, in general, seen higher rates of reactions in younger age groups, so that could be relevant here,” Snape said.
The data have been presented to advisory groups and policy-makers in several countries, including Norway, Denmark “and, indeed in Canada, where this is a relevant question,” Snape said.
“When we talk about vaccines, the top of mind question for most people is, is it safe? And does it work?” Toronto associate medical officer of health Dr. Vinita Dubey said Wednesday during an Ontario Medical Association briefing with reporters.
“This is the first step,” Dubey said, of the Oxford study. “If we don’t have the information for immunogenicity (the immune response) we can at least say, ‘If you get a mixed schedule, it will be safe for you.’ From an individual level, that’s very important, as well as from a population level.”