In clinical trials, multiple leading COVID-19 vaccines were tested as a two-shot regimen. In the real world, three doses have proven to offer strong protection against serious illness. And now, in multiple countries, fourth doses are being explored as a way to ward off waning immunity.
So does that mean you should rush out and get another shot if the opportunity arises? Not necessarily.
The human immune system is a broad, multi-faceted defence network. It starts off rather immature in your infancy, typically sharpens as you age, and tends to struggle more to fight off pathogens in your golden years.
That’s part of the reason there’s no one-size-fits-all answer to getting a fourth dose — since your age is a major factor in how well your immune system responds to the training provided through vaccination.
For anyone who’s at a high risk of getting severe COVID — including older adults, those with comorbidities, and people who are immunocompromised — a fourth shot is likely a “very good idea” and does provide significant additional protection, said Angela Rasmussen, a virologist and researcher with the University of Saskatchewan’s Vaccine and Infectious Disease Organization.
“However, for many people who don’t fit into those categories, it’s hard to say that the fourth shot’s going to provide much of a benefit, especially long-term, over a third shot,” she said.
Study shows 4th shot boosts protection for seniors
In the U.S. on Tuesday, federal regulators authorized a fourth dose of Pfizer-BioNTech’s COVID-19 vaccine for Americans 50 and older, due to concerns about waning immunity in that age group, and for anyone aged 12 and up with compromised immune systems.
Here in Canada, there’s a patchwork approach among the provinces. Several are following the lead of the National Advisory Committee on Immunization, which recommends a fourth shot for moderately to severely immunocompromised individuals six months after their third dose.
Fourth doses are also recommended in Ontario for certain vulnerable seniors, including residents of long-term care facilities, retirement homes, and other congregate assisted-living settings, while Quebec is now offering access to anyone aged 80 and up as well.
And in Israel, where hundreds of thousands have already received a fourth round of the Pfizer-BioNTech shot, a study recently showed it does provide more protection to seniors — including a nearly 80 per cent lower mortality rate from COVID-19 than for older adults who only had three doses.
The country’s largest health-care provider, Clalit Health Services, said the 40-day study included more than half a million people aged 60 to 100. (The findings have not yet been peer-reviewed.)
Close to 60 per cent of the participants had received two booster shots in addition to the basic two-shot regimen studied in clinical trials. The remainder had received just a third dose.
Researchers recorded 92 deaths among the first group and 232 deaths among the second, smaller group.
“The main conclusion is that the second booster is life-saving,” Ronen Arbel, health outcomes researcher at Clalit and Sapir College, recently told Reuters.
New variants may mean new boosters
But multiple outside experts stressed that for most younger individuals, three doses are working just fine to prevent hospitalization and death.
“If you’re a healthy individual, and young, I would not necessarily push very hard for a fourth shot at this time,” said Melanie Ott, director of the Gladstone Institute of Virology and a professor of medicine at the University of California San Francisco.
That could change, she added, if a new variant emerges that’s capable of causing more severe disease, or evading vaccine-driven immunity. If that happens, a new booster for the broader public could become “urgently necessary,” she said.
For now, though, the bulk of the population can rest easy knowing the original vaccines are offering high levels of protection against serious illness — even against the dominant Omicron variant, including highly-contagious subvariant BA.2.
And for those who would benefit from another booster, the question is: Which shot makes sense? Another round of a vaccine designed to fight the ancestral virus, or one tailored for Omicron and its offshoots?
Early findings from a study in monkeys that hasn’t yet been peer-reviewed — which pitted the existing Moderna mRNA-based shot against an Omicron-specific booster — found no major differences in the level of protection, suggesting a radical redesign might not be warranted.
“I think we all thought that [an Omicron booster] would be the superior one, but that does not seem to be necessarily the case,” Ott said. “We might be faring sufficiently well with a fourth shot of the same.”
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Future of vaccination efforts ‘complicated’
There’s also the question of just how long vaccine-driven immunity lasts, and it’s a tough one to answer a little over a year into the global COVID-19 vaccine roll-out.
Right now, it’s not clear whether solid protection spans years, decades — or nowhere close to that.
That potential for immunity to wane against infection or even serious illness, coupled with the possibility of new, unpredictable variants emerging as this virus evolves, means it’s a “very complicated picture moving forward,” said McMaster University immunologist and researcher Matthew Miller.
Coronaviruses do tend to evolve at a slower pace than influenza viruses, he noted, though the sheer number of SARS-CoV-2 infections worldwide has given it ample opportunities to dramatically mutate — and he agreed tailored boosters may be needed at some point down the line.
It’s still unknown, though, whether that would be on an annual or less frequent basis, and if those extra shots would be beneficial to everyone, or just those at the highest risk.
Encouraging ongoing booster uptake could also be a challenge, if the current climate in Canada is any indication. The most recent federal data shows that less than half of eligible Canadians have had three or more doses, compared to more than 80 per cent who’ve had two.
“There’s a lot of work going on thinking about how to operationalize a seasonal COVID vaccine program in concert with our seasonal influenza program… though I think there’s still considerable uncertainty,” Miller said.
Inhaled vaccines that could prevent infections, which Miller is reseaching as part of a Canadian team, might also enter the picture, along with the possibility of so-called “universal” vaccines that would target all coronaviruses or SARS-CoV-2 variants.
Two shots ‘not as good as three’
But while the future of global vaccination efforts remains hazy — with even fourth doses not necessarily needed for the bulk of the population — several experts who spoke to CBC News agreed one thing is clear: It’s worth getting three shots.
“We do actually have quite a bit of evidence now during the BA.1 and BA.2 waves from around the world showing that a third shot really does significantly increase protection against both infection and severe disease caused by the Omicron variant,” Rasmussen said.
The effectiveness of leading mRNA vaccines against emergency or urgent care visits and hospitalizations due to COVID-19 was higher after a third dose than the second, but did wane with time, according to a U.S. Centers for Disease Control and Prevention report released in February.
During the Omicron wave, the vaccine effectiveness against hospitalization was more than 90 per cent during the two months after a third dose, and dropped to roughly 80 per cent by the fourth month.
“Two shots is not as good as three shots,” said Ott. “So at this point, I would definitely encourage everybody to get three shots, because you get an enormous boost and benefit.”
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