NACI guidance based on early research from U.K., Spain that shows mixing shots is safe and effective
Canada is changing its guidelines on mixing and matching second doses of COVID-19 vaccines and is now advising Canadians to combine either the AstraZeneca-Oxford, Pfizer-BioNTech or Moderna shots interchangeably in certain situations.
The National Advisory Committee on Immunization (NACI) updated its guidance to provinces and territories Tuesday and recommended that a first shot of the AstraZeneca vaccine can be followed by either Moderna or Pfizer.
For Canadians who have had a first dose of Moderna or Pfizer, NACI recommends they can now take either of the two shots as a second dose — because they both use a similar mRNA technology — if the same first dose is unavailable or unknown.
The updated NACI guidance is based on emerging research from Spain and the United Kingdom that found mixing and matching AstraZeneca and Pfizer vaccines was both safe and effective at preventing COVID-19.
CBC News first reported the details of the recommendation changes Tuesday morning, based on information from sources with direct knowledge of the decision who spoke on condition of anonymity. The details of the shift in guidance were confirmed publicly by officials from the Public Health Agency of Canada during a news conference Tuesday afternoon.
Canada's Chief Public Health Officer Dr. Theresa Tam said the decision to combine mRNA vaccines interchangeably was "nothing new" and that the same principle had been applied to different types of vaccines in the past — including shots for influenza and Hepatitis A.
"This is not a new concept, so having a multi-dose series in terms of vaccines given by manufacturers is something that public health have used over time for many other vaccines," Tam said. "When vaccines programs and supplies change this is not an unusual thing to do."
The updated NACI recommendations state, "No data currently exist on the interchangeability of COVID-19 mRNA vaccines," but Tam said there are "ongoing studies" on the effectiveness of the approach that have yet to be published. The decision was made based on the similar makeup of the vaccines, which both target the spike protein of the coronavirus, she said.
The recommendations will have a major impact on Canada's vaccine rollout, with previous NACI guidelines stating that a vaccination series that begins with AstraZeneca should follow up with the same type of shot and that mRNA vaccines should only be used interchangeably if the same first dose is unavailable or unknown.
The updated guidelines follow moves by some provinces to combine different shots due to issues with the supply of AstraZeneca and a rare but serious type of blood clot that can result after the shot called vaccine-induced immune thrombotic thrombocytopenia (VITT), which NACI also cited as a reason for its decision in its guidance.
More than 13 million people have received at least one dose of the Pfizer vaccine in Canada, in contrast to over 3.5 million of the Moderna vaccine and more than 2.1 million of the AstraZeneca vaccine as of May 22, according to the latest available federal government data.
Tam said that NACI deemed the "mounting" data on following AstraZeneca with an mRNA vaccine sufficient to update its guidance, and that Canadians need to look at "all the information in front of them" about the risks of the AstraZeneca vaccine.
"The rate of [VITT] after the second dose seems to be lower than after the first dose, but this could increase over time and I think people need to know that kind of information," she said. "Right now it's 1 in 600,000 people who got that second dose that is having [VITT] — but that could change."
Prof. Alyson Kelvin, an assistant professor at Dalhousie University and virologist at the Canadian Center for Vaccinology and the Vaccine and Infectious Disease Organization in Saskatoon said the guidelines were "appropriate" given available data.
Kelvin said she believes the Pfizer and Moderna vaccines could be effectively interchanged because of the similarity between the clinical trial data and the real world research on the two mRNA-based vaccines.
"I don't have any concerns with the mixing and matching, knowing the components of the vaccine," she said, adding there were only slight differences in non-serious side effects with Pfizer having slightly higher reports of mild symptoms. "They're fairly on par."\
Provinces move to change vaccine dose orders
Dr. Zain Chagla, an infectious diseases physician at St. Joseph's Healthcare Hamilton and an associate professor at McMaster University, says the proposed approach to mixing and matching COVID-19 vaccines by NACI is reasonable based on available international data.
"[Pfizer and Moderna] are so interchangeable, I doubt there's going to be any difference between the two," he said. "Their immune responses should be pretty similar."
Manitoba health officials announced Monday that residents who got a first dose of the AstraZeneca vaccine can receive a second dose of either the Pfizer-BioNTech or Moderna vaccine if they meet provincial eligibility requirements.
B.C. Provincial Health Officer Dr. Bonnie Henry said during a press conference Monday that British Columbians who had an initial dose of Moderna or Pfizer will have the option of receiving either mRNA vaccine as a second shot, with more guidance expected this week on AstraZeneca.
Quebec officials announced in April the province would begin administering second doses to its most vulnerable residents — even if the second dose didn't match the first.
The Public Health Agency of Canada (PHAC) now estimates the rate of VITT in Canadians who have received the AstraZeneca vaccine is between 1 in 83,000 and 1 in 55,000, with a fatality rate of between 20 and 50 per cent, but that is subject to change as more data emerges.
PHAC said in a statement to CBC News Thursday there have been 27 confirmed cases of VITT to date in Canada out of two million doses administered, with five deaths among those cases.
Chagla said Canadians who want to have a second dose of AstraZeneca will have access in the coming weeks, but says once supply of Pfizer and Moderna shots are more readily available in Canada it will likely be phased out.
"Second doses make sense," he said. "First doses are starting to get a little bit tricky with so much vaccine coming to Canada."
Kelvin said the future use of the AstraZeneca vaccine needs to "go hand in hand" with the development of a screening mechanism for the condition to identify who's most at risk for the rare blood clots.
"Until we can do that, then we need to at least provide information on what your risk is in general, and discuss using other vaccines as your second dose," she said.
"Having a profile to identify who might be at risk for severe blood clots after the AstraZeneca vaccine would be important moving forward."
Early research shows mixing vaccines safe and effective
The Spanish study that informed NACI's guidance analyzed 670 volunteers between the ages of 18 and 59 who had already received a first dose of the AstraZeneca vaccine, with 450 volunteers given a Pfizer dose.
The study found those who had an initial dose of AstraZeneca vaccine and got a second shot of Pfizer had an increase in IgG antibodies — which are commonly found in the bloodstream and play a key role in creating memory cells that fight the virus — that were 30 to 40 times higher than in a control group who only received one AstraZeneca dose.
Results from the Spanish study were announced in a press conference May 18 and also found the presence of neutralizing antibodies rose sevenfold after a Pfizer dose — significantly more than after a second AstraZeneca shot.
"If you looked at the actual immune response, the study from the Spanish trial showed that if you measure antibody response in someone who got AstraZeneca and then had the second dose as Pfizer — they mounted a really robust immune response," Tam said. "So that boosting response that you want to see is very much present."
The Spanish study also found that just 1.7 per cent of the participants reported severe side effects, which were limited to headaches, muscle pain and general malaise.
Early results from another recent study out of the U.K., which also informed NACI's guidance, found that mixing different COVID-19 vaccines for second doses could increase the chance of someone having mild or moderate reactions like fatigue, headache or a fever — symptoms which could signal a strong immune response.
The findings were published May 12 as correspondence in The Lancet medical journal and came from the Oxford Vaccine Group's Com-Cov vaccine trial, which is studying the use of different combinations of approved COVID-19 vaccines for first and second doses.
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