Canada should investigate mixing doses of different types of COVID-19 vaccines as a way to address shortages and potentially build up more robust immunity to the disease, a vaccine task force member has told The Globe and Mail.
Alan Bernstein, who sits on the federal task force and is CEO of the Canadian-based research and funding organization CIFAR, said the notion of a mixed vaccine regimen was scientifically sound and worth further study. He added that given the urgent state of the pandemic and Canada’s lagging vaccination effort, it’s a strategy that could be assessed relatively quickly in this country with a volunteer-based clinical trial.
The idea would involve supplementing a first dose of a messenger-RNA vaccine produced by Pfizer or Moderna, both of which are authorized in Canada, with a second dose of an adenovirus vaccine from either AstraZeneca or Johnson & Johnson. The latter two are currently under review by Health Canada regulators along with a protein-based vaccine developed by Novavax.
“It’s an excellent idea with a lot of theory behind it,” Dr. Bernstein said.
He added that Canada was particularly well placed to test the mixed regimen option – also known as heterologous vaccination – and should consider doing so or joining forces with a British-based study that was launched last week. That study is seeking to enroll 800 volunteers.
“I think getting volunteers here would be much easier,” Dr. Bernstein said. “There’s a lot of unvaccinated people in Canada, [most of whom] won’t have any hope of being vaccinated for months and months.”
Another advantage is that the fraction of Canadians who have had COVID-19 is relatively small. Any study that weighs the potential risks and benefits of mixing different vaccines would need to follow a cohort of healthy individuals who have so far not been infected by the virus and then study how their immune systems respond to a combination of vaccines when compared to those who are given the same vaccine twice. Unlike a trial that measures vaccine protection, the study would not need to wait to see who gets the disease.
Dr. Bernstein estimated that fewer than 1,000 doses of vaccine would likely be enough to conduct the study.
Canada has already had to diverge from the recommendations made by Pfizer and Moderna based on clinical trials of their vaccines. Both vaccine makers have cut back on orders to Canada and individuals have received first doses without a second dose being held in reserve. According to the companies, those second doses should be given three or four weeks after the first, depending on the vaccine. However, the National Advisory Committee on Immunization has since issued guidelines that say it is accepted to delay the second dose until six weeks after the first.
Caroline Quach-Thanh, who chairs the committee, said she and her colleagues have not yet started to look at the possibility of mixed vaccinations.
“We are looking forward to the U.K. results and have identified this as a research priority,” she said.
Michael Houghton, a 2020 Nobel laureate and vaccine researcher at the University of Alberta, said that he was more comfortable with the idea of mixing two COVID-19 vaccines than he was with delaying the second dose of the same vaccine.
“Given the emergency of vaccine shortages, I think it is okay immunologically to mix and match,” he said.
Dr. Houghton added that while the RNA and adenovirus vaccines use different technologies, they are based on a similar principle of stimulating the body to produce coronavirus proteins, which in turn primes the immune system to recognize a COVID-19 infection.
One potential downside of the strategy would be the risk of exposing individuals to a larger set of side effects than might come from using only one vaccine.
However, there could also be advantages. Some data suggest that the adenovirus vaccines do a somewhat better job of marshalling immune cells know as killer T-cells to fight COVID-19 while the RNA vaccines primarily work by generating antibodies that block the coronavirus. The two together could potentially offer the best of both worlds.
Tania Watts, an immunologist at the University of Toronto, said that it was plausible that such differences might add up in a favourable way, but that more data are needed to be sure.
“I think the idea [of mixed vaccination] is interesting and we need trials to determine optimum strategy,” she said.
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