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The question: The United States is using different Omicron-targeting COVID vaccines than Canada. Which country has the better vaccines?

The answer: The short answer is that we can’t say which vaccines are superior because they have not been studied in head-to-head trials. But what we do know is that there is far more clinical evidence to support the vaccine currently being distributed in Canada.

Throughout the pandemic, SARS-CoV-2 – the virus that causes COVID-19 – has evolved into new variants, some of which can evade the immunity that normally results from a vaccination or an actual infection.

The Omicron variant is a case in point. It has spun off into numerous sub-variants that are highly transmissible.

After Omicron was discovered in November, 2021, some vaccine manufacturers started work on a new type of bivalent vaccine to guard against both the original COVID-19 virus and Omicron.

The new formulations – based on mRNA vaccine technology – contained components of BA.1, the first of the Omicron variants. Patients were recruited for studies to test their effectiveness. At the same time, the companies began seeking approval for their new shots from governments.

However, this past summer, U.S. regulators asked for bivalent vaccines specifically targeting the sub-variants BA.4 and BA.5, responsible for most of their country’s COVID cases.

The change in plans meant that the companies didn’t have time to do human studies. As a result, U. S. regulators had to rely on animal studies when giving their approvals. They assumed that the basic safety of the shots had been established by data from the first generation of mRNA COVID vaccines.

Meanwhile, most other countries – including Canada – stuck with the original BA.1-targeted vaccines, which are backed up by human trials. On Sept. 1, Health Canada gave the green light to Moderna Inc.’s new shot, the first of the bivalent vaccines approved for use in Canada.

To test the effectiveness of the vaccine, blood samples from volunteers who had received the shots were exposed to different variants in the lab.

Results from human trials indicated that Moderna’s vaccine produces neutralizing antibodies against BA.1 as well as against BA.4 and BA.5.

But would the response have been even better if the vaccine specifically targeted BA.4 and BA.5 – as U.S. shots do?

“It is a great question,” said Shehzad Iqbal, the medical director of Moderna Canada. “In all honesty, at this point, nobody would know because nobody has run that in a clinical trial.”

He noted that patient recruitment for a U.S. trial is now under way. Moderna eventually plans to present this study data to Canadian regulators.

Even so, Mr. Iqbal suspects that just having an Omicron component in a vaccine will be enough to generate broad protection against all the existing Omicron sub-variants. “I don’t think it’s ultimately going to make too much of a difference whether or not you have the BA.1 versus the BA.4 or BA.5 target.”

Canadian medical professionals have eagerly welcomed the first of the bivalent vaccines.

“There is clear evidence that the vaccine available in Canada gives you protection against BA.5, which is the dominant circulating version of the virus,” said Dr. Fahad Razak, an internal medicine physician at St. Michael’s Hospital in Toronto.

“If you are one of the millions of Canadians who have been both vaccinated and got infected, this vaccine will improve your antibody response,” added Dr. Razak who is also a professor in the Temerty Faculty of Medicine at the University of Toronto.

The arrival of the bivalent vaccines raises another question: When should you get the shot? Once again, the advice is not the same in the United States as in Canada.

The U.S. Centers for Disease Control and Prevention says that people should wait at least two months since their last COVID vaccine (or three months following a COVID infection) before they receive a bivalent.

In Canada, the National Advisory Committee on Immunizations (NACI) recommends a six-month gap between your last COVID vaccine – or a COVID infection – and the bivalent shot. But a shorter interval of three months may be warranted in cases of “heightened epidemiologic risk.” Those cases might include an immune-vulnerable individual or elevated levels of the virus in the community. The ministries of health in each province and territory are responsible for reviewing NACI’s recommendations and establishing their own guidelines.

There are trade-offs between a long and short wait, said Rob Kozak, a scientist and clinical microbiologist at Sunnybrook Health Sciences Centre in Toronto.

A long interval tends to produce a stronger and more durable immune response. What’s more, he said, your neutralizing antibodies tend to remain fairly high for the first two or three months after a vaccination or infection. So, getting a shot too soon won’t give you much of an added boost in terms of your antibody levels.

On the downside, a long interval can slow the uptake of a vaccine by the public, potentially making the pandemic worse.

“If we are trying to protect people this coming fall and winter, then we want to get as many of them vaccinated with the bivalent as soon as possible,” said Anna Banerji, an infectious disease specialist in the Temerty Faculty of Medicine and the Dalla Lana School of Public Health at the University of Toronto. “So I think the wait should be closer to the three-month mark, not six.”

Indeed, many Canadian experts are worried that we could soon see another big wave of COVID cases, in part, because highly effective public health measures – such as wearing masks indoors – have fallen by the wayside.

To further complicate matters, the health care system could be put under additional strain if lots of people become infected with influenza. For that reason, physicians will be advising patients to also get a flu shot.

Dr. Razak said you could theoretically get both shots together. But annual flu campaigns don’t usually get under way until later in the fall, while a bivalent vaccine is already on hand.

“If you’re in one of the groups that is eligible for the bivalent vaccine, I think it makes sense to get it now because there’s so much of the virus floating around. Then get the flu shot when it’s available,” he added.

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