Canadian researchers have launched a clinical study that could have a direct bearing on thousands of Canadians who received a first dose of the AstraZeneca vaccine and live in provinces that have now stopped offering the vaccine because of its association with very rare but sometimes fatal cases of blood clots.
The federally funded study, which aims to recruit up to 1,300 individuals at six sites across the country, will examine the effects of mixing doses of COVID-19 vaccines.
If the recruitment proceeds swiftly, the study could inform officials involved in the vaccine rollout, along with the National Advisory Committee on Immunization, or NACI, who are looking for data that can show whether such a “mix and match” scenario is acceptable.
“We are aware that provinces and territories will need a recommendation for the second AstraZeneca dose and we are aiming to give guidance in time for [their] decisions,” said Caroline Quach-Thanh, who chairs NACI, an expert panel that provides direction on how vaccines should be allocated.
The new study, which goes by the acronym MOSAIC, is led by the Canadian Immunization Research Network, which organizes clinical studies. In addition to the mix and match question, the study will provide information on the consequences of delaying a second dose by four months, a uniquely Canadian policy that arose from the scarcity of vaccines earlier this year.
“I’m hoping it will help us understand better how to use these vaccines,” said Joanne Langley, a professor of public health at Dalhousie University in Halifax who co-chairs the federal vaccine task force.
In its launch announcement on Thursday, the study team said it is looking to sign up a range of participants who are 18 and over “as soon as possible.”
“The urgency is really because we’re trying to inform the vaccine rollout,” said Manish Sadarangani, director of the Vaccine Evaluation Center at BC Children’s Hospital, who is co-leading the $4.8-million study with Dr. Langley.
The study is designed to test every combination of the vaccines produced by AstraZeneca, Pfizer-BioNTech and Moderna – the only three COVID-19 shots that have been widely distributed across Canada so far. As more vaccines come on line, they could also be added to the study, Dr. Sadarangani said.
To gather data on delayed doses, half of the study group will receive their second dose at four weeks after their first and the other half at 16 weeks.
Most of the participants will have previously had a dose of one of the vaccines. To be eligible that first shot should have been given no more than one month prior to enrolling. The study also requires a smaller fraction of its participants – about 260 people – to be “vaccine naive,” meaning they have not yet received a single shot. These will serve as a reference group, allowing researchers to track their immune responses across the entire vaccination process.
During the study, participants who have already had one jab will be randomly sorted into groups to be given their second. Neither the participants nor those who are administering second doses will know who is receiving which vaccines until the study is complete. Researchers will then gather data on how well the combinations are able to stimulate an immune response in the form of neutralizing antibodies against COVID-19. The study will also compare the strength or severity of any physical reactions that arise as a result of immunization.
“It’s really important that [participants] don’t know what they’re getting because we don’t want how they’re reporting the effects to be based on whatever preconceived ideas they may have about one or other of the vaccines,” Dr. Sadarangani said.
At least two similar studies have preceded the Canadian effort. One, conducted by the Carlos III Health Institute in Spain, released its first results on Tuesday.
The Spanish study, which included about 670 participants, found that individuals who received a second dose of the Pfizer-BioNTech vaccine after a first shot of AstraZeneca had a seven-fold increase in neutralizing antibodies. This is a greater increase than seen in studies of immunity after two doses of AstraZenenca. While antibodies are not a direct measure of vaccine performance, COVID-19 vaccines that are more effective tend to generate higher antibody levels.
A second study, led by a team at Oxford University in Britain, has been following 830 participants since February and is looking at a fuller set of combinations of vaccines. While that study has yet to release data on immunity, preliminary findings published last week suggest that people who received mixed doses of AstraZeneca and Pfizer-BioNTech are more likely to experience adverse reactions, including fever, fatigue, headaches and joint pain.
This was not reported in the Spanish study – an apparent disparity that the Canadian study could help to resolve.
“We’re getting a bit of a mixed message,” said Alan Bernstein, president of the research funding organization CIFAR and a member of Canada’s vaccine task force. “Meanwhile, we have a different population – a more diverse population. So I think it is important that we do these studies rather than just relying on other people’s data.”
Dr. Quach-Thanh said NACI is waiting for the results from the British study, which are expected well before the Canadian study has anything to report.
The challenge for health officials and individuals trying to figure out their vaccination plans is that the Canadian data are unlikely to be available any sooner than July.
Dr. Langley said she and her colleagues have been working to mount the mix and match study for months – a process that has been made slower by Canada’s relatively disconnected public-health and research systems.
That has left provinces and territories in a quandary about how to advise people who have received one shot of the AstraZeneca vaccine.
Some, including Nova Scotia and Ontario, have put the vaccine on hold while awaiting guidance from NACI. Ontario has about 45,000 AstraZeneca doses remaining but expects to receive another 254,500 doses from the federal government this week.
Ontario Health Minister Christine Elliott said she expects guidance on second doses to arrive “well in advance of any expiry date for those doses. Nothing will be wasted.”
Meanwhile, New Brunswick, Alberta and British Columbia are all providing second doses of the AstraZeneca vaccine. “We will continue to ensure we have sufficient supply for dose two for everybody who has received dose one with AstraZeneca,” said Bonnie Henry, B.C.’s Provincial Health Officer. “It is my expectation that people who have received AstraZeneca so far will have a choice once we know more about taking Pfizer or Moderna as the second dose.”
Quebec used up all previous AstraZeneca deliveries on first shots and will use the coming shipment of 148,000 doses to start giving second shots to 200,000 seniors. At each stage, people will be able to opt for Pfizer or Moderna instead as a second dose, the province said.
People who are looking to participate in the MOSAIC study can find more information at cirnetwork.ca/mosaic.
With a report from Les Perreaux in Montreal
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