Why Canada’s Big Bets on Postponing and Mixing COVID-19 Vaccine Doses Could Pay Off

Why Canada’s Big Bets on Postponing and Mixing COVID-19 Vaccine Doses Could Pay Off

Although the typical approach for COVID-19 vaccinations uses the same brand for each dose, given at specific intervals, Canada has considered mixing the doses in addition to delaying second injections for up to four months – two big bets that could pay off.

Before vaccine shipments began to ramp up, Canada’s National Advisory Committee on Immunization (NACI) issued a bold recommendation to delay second doses well beyond manufacturing guidelines for up to four months. .

The movement triggered the criticism that Canada was engaged in a “population-level experiment”, with concerns ranging from a lack of data to a growing body of research suggesting it is not the safest approach for immunocompromised adults and the elderly.

Added to the controversial move are more recent changes to dose blending – including offering an mRNA-based option, from Pfizer-BioNTech or Moderna, to some Canadians who have already had a first injection of ‘AstraZeneca-Oxford.

These measures may seem unorthodox at first glance, several vaccine experts say, but are rooted in decades of science, supported by new research, and could prevent deaths from COVID-19 at a time when Canada is struggling introduce enough vaccines. from abroad.

“I think the single dose strategy, which has been put forward by our Canadian public health agencies, has really saved a lot of lives and has been really instrumental and will be important in getting us back to a more normal life.” said Alyson Kelvin, vaccinologist at VIDO-InterVac, a vaccine development company in Saskatoon.

Mixing doses could also become a useful approach in the coming months, according to Montreal-based cardiologist and epidemiologist Dr. Christopher Labos.

“Mainly because we want people to get their second dose,” he said. “And if supply issues continue to be a problem, we don’t want to delay second doses until the vaccine supply arrives.”

Humber River Hospital healthcare workers administer doses of the Moderna COVID-19 vaccine at a temporary clinic for a member of Toronto’s Spanish-speaking community at the Glen Long Community Center on May 14, 2021. (Evan Mitsui / CBC)

Delaying doses may lead to a ‘better’ immune response

Regarding Canada’s unique approach to delaying doses, vaccine experts pointed out that while it departs significantly from the shorter clinical trial schedule, it fits within the broader framework of the vaccine science.

In general, giving a little more time between a first dose of vaccine and the second dose of vaccine “really leads to a better overall immune response and protection against any pathogen that the vaccine was made against,” Kelvin noted. .

The exact guidelines for various COVID-19 vaccines vary, but one thing is common: Manufacturers’ dosing schedules specify tight deadlines, including two injections just 28 days apart for Moderna, two injections 21 days apart. for Pfizer and two injections at least four weeks apart and no more than 12 weeks for AstraZeneca.

Although manufacturers recommend adhering to clinical trial dosing intervals, those schedules were based on the rapid development of safe and effective vaccines during a global health crisis, and not on determining the best possible delay between doses, Kelvin said.

WATCH | Clinical trials have focused on the “ shortest path to results ” for COVID-19 vaccines, explains the vaccinologist:

While manufacturers recommend adhering to clinical trial dosing intervals, those schedules were based on the rapid development of safe and effective COVID-19 vaccines during a global health crisis, and not for determining the best possible time between doses, explains Canadian vaccinologist Alyson. Kelvin. 0:50

On Friday news broke that a UK study shows Pfizer vaccine generates 3.5 times greater antibody responses in the elderly when a second dose has been delayed to 12 weeks after the first – providing an early indication that a delay may in fact offer more protection. Further research is still needed.

Dr Danuta Skowronski of the BC Center for Disease Control, whose research helped guide Canada’s decision to lengthen the interval between COVID-19 vaccines, told CBC News that the results were not a “surprise”; they pointed out that scientists understood that a longer delay between doses could be beneficial.

The move is also helping Canada quickly vaccinate more residents, with more than half of all eligible adults having received at least one dose to date.

Still, Labs is hoping most Canadians will receive their second dose sooner than NACI’s four-month maximum deadline to ensure they develop strong protection, especially for vulnerable and elderly populations who may experience waning immunity. .

“Four months is probably the outer limit; I don’t think anyone is going to suggest that we push much beyond that,” he said.

“The sweet spot is probably somewhere between that three-week to three-month interval.”

A woman walks past a billboard for COVID-19 vaccines in Montreal on May 14. (CBC / Radio-Canada)

Different vaccines for different doses not “ unprecedented ”

For Canadians who are already wary of a potential delay of several months between doses, the notion of brand mixing – again, an approach not studied in initial clinical trials – might also raise questions.

Even so, various provinces are already taking this route or exploring mixed dosing strategies for the future, given varying supply levels from different manufacturers and ongoing concerns about the risks of rare but serious blood clots from the AstraZeneca vaccine. .

The disease, known as vaccine-induced immune thrombotic thrombocytopenia (VITT), has been reported 28 times across Canada of more than 2.3 million doses of AstraZeneca administered, according to federal public health data, including four deaths.

Several experts pointed out that a mixed dose approach could be useful given the situation in Canada, and is not so unusual for other vaccines.

“Certainly the mixing and pairing of vaccine types is not unprecedented,” noted Matthew Miller, associate professor of infectious diseases and immunology at McMaster University in Hamilton, who is also affiliated with the NACI but not speaking on behalf of the advisory body.

“It’s just that the nature of the situation here is that we have to make these decisions based on ever-changing evidence in the context of an unprecedented public health emergency.

WATCH | Dr Tam discusses second doses, mixing vaccines:

Dr. Theresa Tam, Canada’s chief public health officer, said the government will ensure people can receive their second dose of AstraZeneca’s COVID-19 vaccine and that Health Canada will continue to review studies on mixing vaccines. 1:34

Annual influenza vaccines, for example, can come from a variety of sources, meaning that people might receive a different brand or form of vaccine technology each year. Same with the shingles vaccine, said Miller, who had a formulation in its first generation while a different formulation was used for a later, more effective dose.

“Before that, no one was actually asking, ‘who made my vaccine’, you would just go for a flu shot,” Labs said. “And no one seemed to realize that there were several companies making different types of influenza vaccines, and they were used in different segments of the population – people were relatively oblivious to this whole problem.”

He also noted that the preliminary results from a British study suggest that using different vaccines for different doses might even provide a “better immune response”.

Early findings, based on a trial using the Pfizer and AstraZeneca vaccines, showed that replacing one of each for the two doses increased a person’s risk for mild or moderate reactions such as fatigue, headaches. or fever. These reactions can bode well for immunity, although more research is needed before any definitive conclusions are drawn.

Deaths, hospitalizations among the elderly decreasing

Over the past few weeks, despite questions about Canada’s approaches, it is becoming clear that nation-wide vaccination efforts are starting to bear fruit.

COVID-19 cases, hospitalizations and deaths among older Canadians have recently started to drop at a faster rate than among young adults who are even less likely to be vaccinated, according to CBC News analysis released end of April.

This finding suggests that this country is now following the same path as the United States, United Kingdom and Israel, where mass vaccination campaigns are more advanced and deaths are drastically decreasing.

Overall, Kelvin said Canada’s strategies may raise questions, but nonetheless conformed to a body of vaccine research that existed long before COVID-19.

“I think the fact that all of the evidence we had for COVID-19 vaccines was based on phase three clinical trials was certainly a valid concern,” she said.

“Of course, that didn’t take into account what we understand about vaccines and immune responses to vaccines.”

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