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Benefits and risks of delaying 2nd doses of COVID-19 vaccine

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Federal and provincial health officials are poring over emerging data on the advantages and disadvantages of extending the time between shots of two-dose COVID-19 vaccines. Here are some of the factors they’re weighing and why it matters.

Why do provinces want to space out the doses beyond official recommendations?

More vaccines are arriving and the provinces aim to get them into the arms of willing Canadians as quickly as possible.

But demand exceeds supply, so researchers in British Columbia and Quebec are studying what happens when the interval between doses is extended. That way they can use the supply to vaccinate more people with a first shot sooner.

Late last year, Quebec decided to vaccinate more quickly and more widely by allowing a 90-day delay between doses.

But British Columbia went further on Monday, moving to a four-month interval for doses of the mRNA vaccines from Pfizer-BioNTech and Moderna.

Dr. Howard Njoo, Canada’s deputy chief public health officer, pointed to advances since Health Canada approved those vaccines.

Benefits and risks of delaying 2nd doses of COVID-19 vaccine
A health-care worker prepares to administer a dose of the AstraZeneca-Oxford vaccine, in Santiago, Dominican Republic, in February. (Ricardo Rojas/Reuters)

“What’s happening is, I think, very encouraging,” Njoo said in a briefing on Tuesday.

“We have real-world data, the actual experience of what’s happening with the vaccination, for example in British Columbia and in Quebec, as they’re vaccinating seniors in long-term care facilities. We’re seeing quite a high level of protection.”

Njoo said experts are balancing vaccinating a large number of Canadians to achieve a good level of protection without compromising the effectiveness of the vaccines.

Dr. Sumon Chakrabarti, an infectious diseases physician in Mississauga, Ont., says the top priority is to protect older individuals and those who are at highest risk of severe consequences, hospitalizations and death.

Chakrabarti said the principle of getting as many people covered with one dose is a good one.

“We do know from other vaccines that increase in the interval between two shots doesn’t have any major consequence in decreasing efficacy and in some situations might actually make it better,” he said. “But keeping that in mind, we do have to be careful. I think that we don’t want to stray too far away.”

What’s the basis for the recommended dosing schedule?

Vaccine-makers tested their shots in clinical trials with certain times between doses.

Pfizer-BioNTech’s vaccine is meant to be given as two doses, 21 days apart, while Moderna recommends 28 days. For AstraZeneca-Oxford’s, the interval is eight to 12 weeks.

Health Canada approved the vaccines based on that clinical trial data. Both Pfizer and Moderna acknowledge that, in a pandemic, health authorities will make their own recommendations.

What’s the scientific basis for delaying?

Chakrabarti says there’s evidence, for example, to support delaying the second dose of the Hepatitis A vaccine by six to 36 months, and that’s true for other vaccines, too. But the COVID-19 vaccines haven’t existed long enough to know.

Efficacy for Pfizer-BioNTech’s vaccine was around 95 per cent after both doses and 52 per cent after the first, according to clinical data. For Moderna’s it was about 80 per cent after one dose and 94 per cent following the second.

WATCH | Stop confusing vaccine messaging, expert says:

Benefits and risks of delaying 2nd doses of COVID-19 vaccine

Open communication about evolving decisions around COVID-19 vaccinations is very important to keep public trust, says Dr. Isaac Bogoch, a member of Ontario’s COVID-19 task force. 8:14

The benefits of a second dose include include longer-lasting protection says Tania Watts, a professor of immunology at the University of Toronto who is studying immune responses to COVID-19 vaccines in Canadians. 

She says everyone should eventually get a second dose. But “as we go to the broader population, yes, I think we will still get the benefit if you delay the second dose,” Watts said. 

Watts noted that when the mRNA vaccines were developed, the four-week interval for the “prime-boost effect” in the clinical trials was done for practical purposes.

“All things being perfect, we could stick to the protocol,” from the clinical trials, Watt said. “But, if you can save a lot more lives by not giving everyone the second dose at three weeks, but giving a lot more people the first, I think this is where the rationale comes, and I think it makes complete sense.”

What’s unknown?

The variants of concern that are more transmissible than the original coronavirus could throw a wrench into the works for some combinations of vaccines.

Watts said neutralizing antibodies that block the coronavirus from attaching and infecting cells dropped to almost nil in lab tests of those who received the Pfizer-BioNTech shot against the B1.352 variant that first appeared in South Africa.

“After two doses, which gives you stronger antibodies, you still had some partial protection,” she said.

Watts says Canada is at a critical juncture, watching to see if the variants will take off among partially vaccinated people.

Epidemiological or population-level studies are also needed to figure out how many antibodies are needed to prevent infection as well as the details of immune system memory.

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