What’s the rationale behind a COVID vaccine booster — and will everyone really need one at some point?

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Could “fully vaccinated” soon mean triple vaccinated?

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Israel is prepared to begin declaring the COVID-19 “passports” of more than one million vaccinated Israelis null and void, after making boosters — third doses — a requirement for full inoculation, the New York Times and Financial Times reported Sunday.

Israel was the first country in the world to make boosters of the Pfizer vaccine available to the entire population. The United States has also begun a booster rollout while Canada’s immunization advisers are mulling just how far to endorse the use of third doses.

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Some fear the push to boost risks undermining confidence in the shots and that the unvaccinated will see it as evidence COVID-19 vaccines aren’t working. “Many of my patients are already saying, ‘If we need a third dose, what was the point,’ ” Dr. Jason Goldman, a doctor in Coral Springs, Fla., told the Los Angeles Times. Others say the issue shouldn’t be positioned so much as “booster” shots, but rather that a third shot is about “completing” vaccination. “We may have found ourselves using two shots when we really needed three,” bioethicist Arthur Caplan has argued.

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Durability is driving the debate: Emerging evidence suggests a “modest waning” in protection against infection, American and British researchers wrote in a recent editorial in the British Medical Association Journal. An extra dose seems entirely prudent for the elderly and those with compromised immune systems, who tend not to mount as robust an immune response to vaccines, they said, “But overstating evidence of waning immunity for the general population has already had important ramifications, including affecting vaccine confidence.”

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“Most importantly, the long term effects of boosters on reducing infection, transmission and hospital admissions remains unknown.”

Canada’s National Advisory Committee on Immunization has recommended boosters for a select group, including residents of long-term care and seniors living in congregate settings at high risk of exposure and serious sickness from COVID. NACI also recommends boosters for people with weakened immune systems.

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The U.S., meanwhile, has begun offering boosters amid “chaotic” and confusing messaging, after the head of the Centers for Disease Control and Prevention overruled her own board of advisers and granted emergency use authorization of boosters for people in high-risk jobs and those with underlying health conditions, not just the 65-plus. The United Kingdom is deploying third doses for Britons over 50, to be given at least six months after a second shot of either Pfizer or AstraZeneca’s COVID vaccine. And on Monday, the European Medicines Agency is expected to weigh in on the need for Pfizer boosters for the general population, Reuters reported.

The prospect of potentially endless boosters has led to protests in Israel. However, a large study involving more than one million people in Israel aged 60 and older who received at least two doses of the Pfizer vaccine found that the rate of confirmed infection was 11 times lower in the boosted group, versus the non-boosted. The rate of severe illness was lower by a factor of nearly 20. The boosted 60-plus had higher blood levels of antibodies.

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“Israel is becoming everybody’s crystal ball, because they were so early — they got out before anybody with really aggressive vaccination programs,” Rodney Russell, editor-in-chief of the journal Viral Immunology and a professor of immunology and virology at Memorial University of Newfoundland, said in a recent interview.

“The rest of us can watch what happens in Israel, to try to figure out what’s going to happen locally. And what’s happening in Israel now is, we are seeing breakthrough infections.” After a period with almost no confirmed COVID, Israel saw a resurgence this summer. The breakthrough cases have been primarily in older, more frail people with other health conditions, Russell said.

Antibodies typically peak two weeks after vaccination, or a natural infection, but then eventually begin to tail off. “The immune system does stop pumping out tonnes of antibodies” once the reaction to the vaccines subsides, Russell said. “And it’s the level of antibodies that are probably keeping you from getting infected.”

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But the real workhorses are memory B cells, which can rapidly churn out antibodies if the person is re-exposed to SARS-CoV-2, and memory T cells, which act in a similar way. Memory cells can last for a decade or longer. They kick in quickly after re-exposure, “quicker than the first time, and you’ll have antibodies made within days,” Russell said.

It likely explains why breakthrough infections are not as intense, or as contagious. “Even though you might get infected, you’re not as sick, and you’re probably not going to spread,” Russell said. Vaccine effectiveness against serious outcomes remains “very high,” Canada’s chief public health officer, Dr. Theresa Tam, said in mid-September.

A third dose tweaks the antibody level, bumping it up. But eventually, that too will peter out. A booster might also produce more longer-lasting memory cells, though the authors of the BMJ editorial said that remains unproven for most “immunocompetent people.”

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It’s not known whether there would be an increased risk of myocarditis, or other rare reactions after a booster dose. Data from Israel, where more than three million have been vaccinated with a third COVID shot, suggest fewer side effects such as fatigue, weakness and pain in the injection site after a third dose versus the second, the Times of Israel reported. The CDC also has not seen evidence of “unexpected patterns” of side effects after a booster dose of an mRNA vaccine among more than 12,000 people who have received one.

The SARS-CoV-2 virus is changing. “We may all need a third shot at some point,” Russell said. “I don’t see it like a six-month thing, or every year, but honestly, no one really knows. It’s still a wait-and-see. And will everyone need one? Maybe people under 30 won’t need them, maybe people under 40 won’t need them. Maybe everyone over 60 should get one every year.

“I don’t think there’s going to be a one-size-fits-all on boosters.”