Data in favour of mixing COVID-19 vaccines, but long-term effects unknown: experts

Canada, like several other countries, has been mixing and matching COVID-19 vaccines for weeks amid safety concerns over the AstraZeneca shot.

On Monday, the chief scientist at the World Health Organization (WHO) cautioned against that approach, calling it “a dangerous trend” for a subsequent dose as well as booster shots saying there was insufficient evidence available about the health impact.

“There is limited data on mix and match,” said Soumya Swaminathan during a virtual news conference.

“Maybe it will be a very good approach but at the moment we only have data on the Oxford-AstraZeneca vaccine followed by Pfizer,” she added.

However, her concerns stemmed from individuals deciding to mix vaccines or take additional doses on their own without public health guidance.

In Canada, the National Advisory Committee on Immunization (NACI) has recommended since June that people who received a first dose of the AstraZeneca vaccine should get an mRNA vaccine — Pfizer-BioNTech or Moderna — for their second dose, unless contraindicated.

People who have received a first dose of an mRNA vaccine should be offered the same vaccine for their second dose, NACI said. But mRNA vaccines can be interchangeable if the same product is not readily available for the second dose, it added.

The non-binding recommendations were based on a range of factors from safety concerns to vaccine supply, said Theresa Tam, Canada’s chief public health officer, during a news conference on June 1.

Since then, several provinces have deployed the strategy in their vaccine rollout.

1:57 NACI recommends Pfizer or Moderna for people who received AstraZeneca as first COVID-19 vaccine shot

Some Canadian experts say the benefits of mixing doses outweigh the risk and there is enough evidence in favour of the approach.

“There’s real-world data in Canada … that suggests that mixing vaccines is quite effective at producing good antibodies against SARS-CoV-2,” said Alberto Martin, a professor of immunology at the University of Toronto.

While some countries in the Middle East have started offering a third booster shot to its residents, Canada is not recommending doses beyond the second one at this point.

Joanne Langley, a pediatric infectious diseases expert at Dalhousie University, said there was no data so far to suggest that a different second dose was harmful.

“There’s some evidence that it could work as well as the same vaccine and in the case, if you got the AstraZeneca first, it may work better to have mRNA (as a second dose),” she told Global News.

In making its recommendation, NACI cited early data from Europe that suggested that mixing doses of COVID-19 vaccines is safe and effective.

Preliminary results from a University of Oxford study published on May 12 found that mixing the Pfizer-BioNtech and AstraZeneca COVID-19 vaccines may increase the frequency of mild to moderate side effects. But these symptoms were short-lived — lasting no longer than a few days — and there were no hospitalizations or other safety concerns.

Meanwhile, a Spanish study released on May 18 showed that the presence of neutralizing antibodies rose sevenfold after people who already received a first shot of AstraZeneca vaccine were given the Pfizer dose, significantly more than the doubling effect observed after a second AstraZeneca shot.

Another study in Germany — not yet peer-reviewed — found that mixing vaccines was better at inducing an immune response than giving two AstraZeneca shots. Overall, the incidence of any systemic reaction was less common after the mixed series.

2:09 Experts question Pfizer’s calls for third COVID-19 vaccine dose

NACI’s recommendation also took into consideration the risk of blood clots following the AstraZeneca vaccine.

While there is no current data on the interchangeability of mRNA vaccines, NACI said there is no reason to believe that mixing Pfizer and Moderna shots would result in any additional safety issues or deficiency in protection.

Canada is not alone in endorsing the mix-and-match regimen.

On June 15, the Strategic Advisory Group of Experts on Immunization (SAGE) that advises the WHO gave permissive recommendation to use the Pfizer vaccine as a second dose following a first dose with the AstraZeneca vaccine if a second dose of AstraZeneca vaccine was not available due to supply constraints or other concerns.

Several European countries, including Denmark, Finland, France, Germany, Norway, Spain and Sweden, have also offered a second dose of an mRNA vaccine to those who received a first dose of AstraZeneca.

While the preliminary data is promising, experts warn that there are still many unanswered questions when it comes to the long-term impact of mixing doses.

“There might be some long-term health effects of mixing and matching vaccines,” said Martin.

“There’s no real reason to believe that there should be a problem, but you just never know sometimes.”

2:03 Do Canadians need a 3rd Pfizer shot?

Tania Watts, an immunologist and professor at the University of Toronto, said more information is needed to determine when a booster shot can be given and what the best combination of vaccines are to elicit the “longest lasting and most effective immunity.”

Langley agreed.

“We still have a lot to learn and we need to have research programs in place to study the long-term safety, immunogenicity and effectiveness of these mixing and matching of vaccines,” she said.

— With files from Global News’ Jamie Mauracher.