Here’s what you need to know about 4th doses of COVID vaccine

If you’ve heard that Israel is well underway administering fourth doses of COVID-19 vaccine, you may be wondering if it will soon be time to hunt for another vaccine appointment yourself.

It’s long been the plan to offer immunocompromised Canadians a three-dose primary series of shots followed by a booster, but it’s not clear yet that a fourth round of vaccine is necessary for the broader population.

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Israel’s situation is a little different, explains virologist Darryl Falzarano, a research scientist at the University of Saskatchewan in Saskatoon, who studies virus transmission as well as immune response to infection.

“Israel’s vaccine campaign started earlier, so they’re longer out from their third dose than a lot of other places, so they’re in a slightly different position,” said Falzarano, who is also a deputy with the Coronavirus Variants Rapid Response Network (CoVaRR-Net), a group of researchers that advises the federal government on how to respond to SARS-CoV-2 variants.

Darryl Falzarano, a research scientist at the University of Saskatchewan in Saskatoon, said we’ll need a lot more data before it’s clear whether a fourth dose of COVID-19 vaccine will make a significant difference. (David Stobbe/StobbePhoto.ca)

Israel started administering boosters in late July, which means immunity from that booster is more likely to be waning there just as the Omicron variant has sent cases skyrocketing around the globe.

Israel is now offering fourth doses to everyone over 60, immunocompromised people and health-care workers. Its health ministry said Friday it had administered more than 500,000 fourth doses.

Do fourth doses help?

It’s too soon to say, but Israel has been right about boosters before.

“I think they were right on the third dose potentially really being necessary and useful at that five- or six-month mark,” said Falzarano, who holds a PhD from the Department of Medical Microbiology at the University of Manitoba. “But we’re really going to have to wait to see … whether a fourth dose is really needed and whether a fourth dose is going to help.”

Only once enough time has passed — likely at least a few months — will researchers know whether people who received fourth doses had more protection against infection, severe illness and hospitalizations than those with three.

Dr. Isaac Bogoch, an infectious diseases specialist based out of the Toronto General Hospital, called that “the million-dollar question.”

While there are only “small shreds” of data about the efficacy of fourth doses available, the theory is that certain groups might benefit from a fourth dose, Bogoch told Dr. Brian Goldman, host of CBC podcast The Dose — for example, the immunocompromised and the elderly.

“It looks like all arrows are pointing in the direction, even in Omicron, that three doses is better than two,” said Bogoch, who is also a member of Ontario’s COVID-19 task force.

A health-care worker prepares a dose of the CoronaVac COVID-19 vaccine in Santiago, Chile, in February 2021. Both Chile and Brazil are now underway with fourth-dose campaigns. (Esteban Felix/The Associated Press)

“The question here is what is the meaningful short-term, medium-term and long-term protection that a fourth dose affords [a person], versus three doses?”

How will we find out more?

Falzarano said researchers will be studying people’s antibody levels in the months following a third dose. It’s expected that antibody level jumps after a vaccine, then slowly wanes in the months to follow. But the picture four to six months down the road is key, he said.

“If it drops from 90 to 87 [per cent effectiveness], I don’t think we’re going to be concerned. If it drops from 90 to 20, that’s a big difference. Something like that would easily justify a fourth dose,” Falzarano said.

Bogoch said he hopes the fourth doses administered in places like Israel — and even in Ontario, where they’re now being offered to some immunocompromised people and long-term care residents — are carefully tracked so there’s high-quality data to help shape policy moving forward.

Are boosters adapted for new variants?

So far, not yet. Falzarano said some vaccine makers have reformulated their shots to new variants, but these aren’t the ones in use right now. 

“Both Pfizer and Moderna did make Beta- and Delta-specific vaccines,” he said, noting that, prior to Omicron, Beta was the variant most likely to overcome the protective effects of the vaccines. 

A person receives a shot during a drive-through COVID-19 vaccine clinic in Kingston, Ont., in January. Ontario is in the midst of administering third booster doses, though some immunocompromised people will be offered a fourth dose. (Lars Hagberg/The Canadian Press)

But in some small clinical trials, the Beta-specific vaccine did not seem an improvement on a boost with the original vaccine, said Farzarano. However, vaccine makers are still working to keep up with variants.

“Pfizer’s already talking about making an Omicron vaccine that’s supposed to be available in March, although other people say that more realistically would be … in June.”

There’s also the question of whether a new variant of concern will have stolen Omicron’s thunder by the time companies formulate and trial new Omicron-specific vaccines.

Shouldn’t these doses go to poorer countries? 

When the Omicron variant was discovered in South Africa, where vaccine uptake hovers around 28 per cent, the world learned how little it can afford to leave poorer nations behind.

Only about 50 per cent of the world’s population is fully vaccinated with two doses, said Farzarano. “That’s clearly leaving a huge vulnerable population to make new variants in.”

Infectious diseases specialist Dr. Isaac Bogoch says countries can still roll out third doses while making regular donations to COVAX, the global initiative managing distribution of COVID vaccines to the rest of the world. (Submitted by Isaac Bogoch)

Bogoch said wealthy countries should ask themselves, “Are you giving third and fourth doses at the expense of many places on Earth that haven’t even given a first and a second dose?”

He said countries can still roll out third doses while making regular donations to COVAX, the global initiative managing distribution of COVID vaccines to the rest of the world.

Will COVID boosters become like flu shots?

While it may feel as though we’re on a never-ending quest for COVID-19 vaccines, Farzarano points out that the current series — two primary shots close together followed by a booster six months or more down the road — “is a pretty typical vaccination schedule for a lot of vaccines,” including those for polio and HPV.

It’s not known yet whether, going forward, we’ll need annual COVID vaccinations akin to flu shots, or perhaps a boost every two or three years, said Bogoch.

He said vaccinating people every four to six months moving forward is “obviously not a sustainable or smart approach,” especially given evidence that variants will crop up that make it impossible to stamp out infections altogether.

Bogoch said the focus should be on preventing people from getting really sick.


Written by Brandie Weike, with files from Associated Press. Produced by Colleen Ross and Brian Goldman, with help from Amina Zafar.


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