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A syringe is prepared with the Pfizer/BioNTech COVID-19 vaccine at the Norristown Public Health Center in Norristown, Pa., on Dec. 7.Matt Rourke/The Associated Press

The question: I’ve had two doses of a COVID-19 vaccine and I thought I was fully inoculated. Now some provinces are rolling out booster shots. Is this going to turn into an every-six-months thing?

The answer: There is still a lot we don’t know about COVID-19 and the emergence of new variants of the coronavirus – most recently Omicron – only adds to the uncertainty.

Canada’s National Advisory Committee on Immunization, a federal panel that provides advice to provinces on new vaccines, has strongly recommended that people 50 and older get a COVID-19 booster shot at least six months after their second dose. It has also said people 18 to 49 may receive a booster depending on various risk factors, such as local transmission rates, evidence of waning immunity or certain medical conditions.

It’s possible that more booster shots will be needed, but who should get them and how often is anyone’s guess.

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It is important to keep in mind that the vaccines were developed in record time – and they represent a remarkable scientific feat.

The initial trials were focused on effectiveness and safety. In the case of the messenger-RNA vaccines – such as those produced by Moderna and Pfizer/BioNTech – two doses creates a very strong defence against SARS-CoV-2, the virus that causes COVID-19.

“Because the manufacturers urgently needed to get the vaccines to market, they didn’t have the luxury to wait and see if that immunity was durable,” says Andrew Morris, an infectious-diseases physician at Sinai Health and the University Health Network in Toronto.

He notes that many other vaccines require three shots to produce long-lasting protection. Vaccines for hepatitis B, the human papillomavirus, as well as mumps, measles and rubella all require three doses.

“The body’s immune system often needs to be reminded numerous times,” in order to effectively recognize an enemy and then develop sufficient defences to guard against subsequent attacks, explains Dr. Morris.

Why some vaccines work with just one dose while others need multiple shots is not fully understood, says Jen Gommerman, a professor of immunology in the Temerty Faculty of Medicine at the University of Toronto. “It’s still an area of active research,” she says.

To further complicate matters, the main COVID-19 vaccines approved for use in Canada are based on relatively new vaccine technology.

“We’re in uncharted territory and we are trying to carve out a path as new information comes in,” says Jason Kindrachuk, a virologist at the University of Manitoba.

However, he adds, we can get some idea of what to expect by looking to other countries where COVID-19 booster shots have been administered for a longer period of time.

For example, in Israel – which has one of world’s higher vaccination rates – there was marked rise in “breakthrough” infections in people who were considered to be fully inoculated.

Israel then became the site of a clinical trial in which volunteers over the age of 60 were given booster shots.

“They found that the additional doses significantly lowered the likelihood of getting an infection and developing severe disease,” said Rob Kozak, a clinical microbiologist at Sunnybrook Health Sciences Centre in Toronto.

So, the extra shots clearly bolstered immunity. But the question remains: for how long?

A vaccine – whether it involves one or more jabs – essentially trains the immune system to be on the lookout for a particular pathogen and to be ready to spring into action when challenged.

So-called “neutralizing” antibodies are the first line of defence. They will latch onto an intruder virus and prevent it from invading the body’s cells. Other antibodies will tag viral particles and mark them for elimination by different immune cells.

If a virus does evade the antibodies and actually enters a cell, killer T-cells can destroy the infected cell to prevent the virus from replicating.

Once an infection is under control, the number of specialized antibodies to deal with this particular threat will gradually decline.

“The immune system is smart,” explains Dr. Gommerman. “It sees no reason to spend a lot energy producing a super high level of antibodies which are no longer needed.”

Low levels of the antibodies will continue to be churned out by bone marrow for years to come. But the most critical ongoing protection is provided by memory B cells, which circulate in the bloodstream.

If they spot the virus again, “the memory B cells get quickly reprogrammed into antibody-producing cells,” says Dr. Gommerman. “They become the source of a sudden elevation in antibodies.”

Dr. Kozak noted that each encounter with a specific foe becomes a learning experience for the immune system – and the memory B cells get better and better at identifying and neutralizing the threat.

This improvement happens regardless of whether it’s a live virus or a harmless representation of one contained in the vaccine.

Similarly, with both a real virus and a vaccine, there will be a rise and subsequent fall in antibody levels in the bloodstream.

And that pattern has been observed in people who have received COVID-19 vaccines.

After a shot, their antibody levels will suddenly spike. Over a period of months, the levels will gradually diminish.

“As our antibodies decline, we could become susceptible to breakthrough infections,” says Dr. Gommerman.

Although the memory B cells are primed and ready for action, it still takes them several days to rebuild antibody stores.

In the meantime, a person with a breakthrough infection could spread the virus to others.

Dr. Gommerman points to the example of Colin Powell, the former U.S. Secretary of State who recently died of COVID-19 complications. He had been double vaccinated. But he was also receiving cancer treatments, which suppressed his immune response to the inoculations.

A mass campaign to provide booster shots will temporarily raise antibody levels among those who are vaccinated and that may help slow the spread of COVID-19 in the community during the coming winter months.

But the biggest threat of community spread comes from the large group of people who have not yet received any vaccines, says Dr. Gommerman.

Another wild card is the potential evolution of new variants that may be able to escape the defences of our existing vaccines. In the case of Omicron, there is some promising preliminary evidence that booster shots may help neutralize the virus.

Experts also point out that immunity from certain infectious diseases can wane over time.

“We may find that boosters provide us with protection that lasts a long time. But we might also find that we need a shot every year,” says Dr. Kozak.

He said annual COVID-19 boosters could end up resembling seasonal flu shots. They might be modified to deal with the latest variants in circulation or targeted at vulnerable individuals.

“To be honest, I would be hesitant to say what it’s going to be because we just don’t know enough yet.”

Paul Taylor is a former Patient Navigation Adviser at Sunnybrook Health Sciences Centre and former health editor of The Globe and Mail.

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