The next stage in the battle against COVID-19: bivalent vaccines

Predictions of a wave of COVID-19 in the fall make another booster vaccination campaign likely, but questions abound about how the virus will continue to evolve and what protections a new vaccine might offer.

Several vaccine manufacturers are racing to develop formulas that take into account the most infectious variant of Omicron now driving cases, while policymakers are laying the groundwork for another large-scale vaccine blitz.

Much of this hinges on expectations that a so-called bivalent vaccine could blunt a potential future surge as flu season kicks off and ease pressure on a strained health care system.

The National Advisory Committee on Immunization last week released interim guidelines for a fall schedule that it said was most important for older adults and those most at risk of severe COVID-19. He also noted that while the vaccine’s protection against symptomatic disease declines over time, protection against severe disease is better maintained.

In the United States, Food and Drug Administration advisers said last week that fall boosters should contain some version of the Omicron variant.

NACI stopped short of urging a specific formulation while waiting for more evidence, but said a bivalent injection could encourage uptake in the fall.

Here’s a look at the next stage in the fight against COVID-19.


Currently available COVID-19 vaccines are monovalent, designed solely for the original novel coronavirus. The proposed bivalent vaccines target specific mutations in the spike protein that are seen in both the old strain and the newer Omicron strain, which itself has spawned several other infectious subvariants that dominate infections today.

In essence, bivalent vaccines are a split between the old “original” mRNA sequence and the new sequence, says Dr. Zain Chagla, an infectious disease specialist.

“So, for example, Moderna’s bivalent is an old 25mcg vaccine, an updated 25mcg vaccine,” he says.

The basic principle is already well established with the flu vaccine, says immunologist and University of Toronto professor Tania Watts.

“With the flu, we do three or four different variants. It’s just a mix, and RNA vaccines are very easy to mix and match. In theory, we could have 10 (specific variants),” Watts says.

“And I think that’s the future. People aim to get a universal vaccine.


Experts say Canada is already in the midst of its third Omicron wave, which could be followed by a new variant COVID-19 threat, but that doesn’t necessarily make an Omicron-modified vaccine out of date if it doesn’t land until the fall.

Dr. Volker Gerdts, director and CEO of the Organization for Vaccines and Infectious Diseases, says the best strategy is to provide as broad protection as possible.

“That’s why some of these so-called bivalent vaccines still have the original strain and then an additional Omicron or Delta with it,” says Gerdts.

“The overall goal is to have multiple different types in your vaccine to provide broad protection.”

Part of the difficulty in testing new vaccines is comparing them to variants that don’t even exist, he says.

“If we have very different strains, or different variants, in this representation of vaccines, then we can assume that we will also get broad protection against future variants,” he says.

Pfizer Canada and Moderna Canada say their mRNA platforms allow rapid updates to address new variants if necessary.

But it’s possible that “bivalent boosters provide broad protection against several different variants, even those that weren’t specifically designed to fight,” Shehzad Iqbal, chief medical officer for Moderna Canada, says by email.


There is some uncertainty here, says Chagla, a professor at McMaster University in Hamilton.

The evidence so far is that they can increase antibody levels more than previous doses. But he says there’s no clinical data to illustrate exactly what that means: Does that translate to longer protection against symptomatic disease? Even more protection against hospitalization? How long do the effects last? Will they decrease over time?

“There are no guarantees with this reinforcement coming,” says Chagla.

“My guess is that it will probably extend the benefits for symptomatic infection beyond eight weeks, nine weeks, 10 weeks.”

He suspects they will behave in the same way as current COVID-19 injections: the induced antibodies will decay over time, and people can be reinfected.

To complicate matters, the virus continues to evolve, adds Chagla.


Moderna Canada says it submitted its bivalent booster candidate to Health Canada on June 30 for regulatory approval. Iqbal says the proposed update is a 50mcg dose containing the original vaccine, known as Spikevax, and a vaccine candidate targeting Omicron.

“While we cannot speculate on the timing of Health Canada’s review, our goal is to have the Omicron-containing bivalent booster available by early fall 2022,” says Iqbal.

Pfizer Canada also said it plans to seek approval for another COVID-19 vaccine.

“We are currently in discussions with Health Canada to prepare to submit our available data, including data for constructs that include the Omicron BA.1 or BA.4/5 subvariants,” the company said by email.


If bivalent injections are ready by the fall, infectious disease expert Dr. Isaac Bogoch hopes we can run three vaccine programs simultaneously: a booster program, a COVID-19 vaccine program for children under six if they are also approved; and the annual influenza vaccination program.

“One of the challenges is that in much of the country much of the infrastructure for mass vaccination has been removed,” says Bogoch, a professor at the University of Toronto.

“Most vaccines are now being administered in traditional settings like primary care clinics and public health clinics and pharmacies. So it’s probably going to be a very busy time.”

Chagla adds that there are many moving parts to ensuring a smooth rollout of the vaccine, as seen in the rocky days of Canada’s first big push to put needles in arms: “It’s not as simple as the vaccine drops and everyone has access, right?

“You have to scale up, and often it takes people away from their day jobs, it takes doctors away from their patients and nurses and other valuable healthcare personnel away,” says Chagla.

Such drives should be timed to deal with an increased risk of infection, he adds, making fall probably the best time to boost population immunity, ahead of the rise in indoor and seasonal gatherings.


Bogoch and Chagla point to steady advances in technology that could shape the coming years, including work to develop needle-free intranasal vaccines.

“And that could be very promising because it really targets what’s called the mucosal immune system. And that could allow us to better prevent infection in the first place,” says Bogoch.

Along with Gerdts, they also touted efforts to create pan-corona vaccines that can provide protection against multiple types of coronavirus.

Gerdts says such a product would likely include structures from many different members of the coronavirus family, not just the SARS-CoV-2 that causes COVID-19, but also perhaps Middle East respiratory syndrome, also known as MERS, and another common respiratory coronavirus. .

“The more distant the members you have in your vaccine, the broader the level of protection against new variants originating from them,” says Gerdts, who was scheduled to attend a meeting in Washington on Thursday and Friday organized in part by the National Institutes of Health to decide how to protect against future variants.

“If a virus mutates and evolves further, it has to start somewhere and so by going with existing ones, but pick a few that are too far apart so you’ve already evolved quite a bit, you’re likely to catch all of these new mutants that could emerge in the middle”.

Such a vaccine is still years away, he adds.

“A lot of this is really about predicting today what tomorrow’s pathogen may be.”

This report from The Canadian Press was first published on July 7, 2022.


What questions do you have about travel rules amid COVID-19? wants to hear from Canadians if they have any questions.

Tell us what you would like to know about the rules for entering or leaving Canada.

To submit your question, email us at [email protected] with your name, location, and question. Your comments may be used in a story.

Leave a Comment