With kids and teens back in school, students at university, Canadians spending more time indoors in the workplace and at social gatherings, and new variants always lurking, an 8th wave of COVID-19 is expected this fall. It’s not yet known how fast or how tall this next wave will be or whether it will be driven by a new variant or by waning immunity against the variants already present.
A new bivalent vaccine targeting both the original “Wuhan” virus and the BA.1 subvariant of Omicron has just been approved by Health Canada. While this vaccine has been shown to boost immunity in humans, the U.S. has already approved the next-generation bivalent targeting BA.5 instead, based on trials in mice. Should Canadians wait to get their next booster until a BA.4 or BA.5 bivalent vaccine is approved and available? Should they get vaccinated with the recently approved bivalent against BA.1? Should they get a booster of an existing monovalent COVID-19 vaccine if that’s all that’s available when they are eligible? Or should they wait for a vaccine that works on all coronaviruses?
“If you are a young, healthy adult or a child, the BA.1 bivalent provides nearly equal protection against BA.1 and BA.5, based on the breadth of antibodies. For this reason, we recommend the recently approved bivalent, even though BA.5 is now the dominant variant in Canada,” says Dr. Ciriaco Piccirillo, Co-Lead of CoVaRR-Net’s Immunology & Vaccine Protection Pillar, Senior Scientist at the Research Institute of the McGill University Health Centre, and Professor, McGill University. “That said, even the original (monovalent) vaccines provide a major boost – the BA.1 bivalent offers only a modest additional boost. What is important, is to get protected with whatever booster is available, particularly at the beginning of this next wave to maximize protection.”
“The existing monovalent vaccines still give you strong protection against severe disease, hospitalization, and death,” he continues. “That protection doesn’t disappear against new Omicron subvariants, such as BA.5, although it is reduced. If the bivalent booster is available to you, get that one. If the bivalent isn’t available and you don’t know how long you’ll have to wait, get the one that’s available,” he advises.
What is a bivalent vaccine?
Bivalent COVID-19 vaccines are similar to the original RNA vaccines produced by Pfizer and Moderna but encode instructions to make two different versions of the virus’ spike protein. This primes the immune system to better recognize different SARS-CoV-2 variants.
On September 1, 2022, Health Canada approved the first bivalent vaccine, which targets both the original strain and the Omicron BA.1 subvariant, following studies demonstrating safety and superior antibody protection in humans. In June, however, the U.S. FDA and Health Canada both asked Pfizer and Moderna to reformulate their boosters to target the new BA.4 and BA.5 subvariants dominant in Canada and in much of the world.
Both manufacturers returned in late August with these new anti-BA.4 and BA.5 versions, with performance data in mice. Based on this lab data and the similarity between a bivalent targeting BA.5 versus BA.1, the U.S. FDA approved the newer bivalent last week. It is unclear when the anti-BA.4 and anti-BA.5 versions will be approved and available to Canadians.
“Given that this is the first bivalent booster ever used against COVID-19, it seems prudent to wait for additional safety and efficacy data in humans before rolling out the bivalent targeting BA.5,” says Dr. Sarah Otto, Co-Lead of CoVaRR-Net’s Computational Analysis, Modelling and Evolutionary Outcomes (CAMEO) Pillar and Killam University Professor at the University of British Columbia.
How well does the bivalent targeting BA.1 work?
Data presented by Moderna found no difference in safety between the original and bivalent vaccines and no serious adverse reactions related to either vaccination.
“How well the vaccine works was assessed by collecting blood from people following vaccination and measuring the concentration of antibodies able to neutralize SARS-CoV-2 (i.e., prevent the virus from infecting cells). Antibodies able to neutralize BA.1 had 1.75-fold higher concentrations in blood from people who had received the bivalent booster, compared to blood from people boosted with the original Moderna vaccine. This demonstrates that the immune system had better adapted to target BA.1 after the bivalent vaccine,” says Dr. Otto.
A similar improvement was seen against BA.5, with a 1.69-fold rise in neutralizing antibody titers following the bivalent booster approved in Canada compared to a booster with the original vaccine, according to a National Advisory Committee on Immunization (NACI) report.
While these results demonstrate that the bivalent approved in Canada better protects against Omicron variants, getting a booster with the original vaccine is still much better than no booster at all: a booster with the original vaccine still raises neutralizing antibody levels against BA.1 3.8-fold.
There is an urgent need for a pan-coronavirus vaccine that reduces transmission and infection rates
The issue, of course, is that the new bivalent boosters are tailored towards the specific spike proteins present in BA.1 or BA.4/BA.5 sampled months ago, as well as in the Wuhan variant sampled from early in the pandemic. As the virus continues to evolve, we may not be much further ahead.
Two approaches to pan-coronavirus vaccines are in development. One is to find parts of the virus that remain the same over evolutionary time, even among different coronaviruses. These pan-coronavirus vaccines could theoretically work against various types of coronaviruses and may offer broad and durable protection against infection and severe disease from new variants.
“The next generation of coronavirus vaccines will target not just the spike protein but also some non-spike proteins of the virus that our immune system can recognize, which are more conserved or don’t mutate as much as the spike protein. Together, as a cocktail, antibodies induced to these various proteins would bind to the virus and help the immune system to more easily identify cells infected by new variants and other types of coronaviruses. That would be a game-changer,” says Dr. Piccirillo, who is doing research to find molecular components that could be integrated in future multivalent or pan-coronavirus vaccines.
A second approach is to boost immunity where the virus first enters our bodies, using sprays delivered through the nose or mouth. More than a dozen nasal sprays are being tested in clinical trials around the world, including one CoVaRR-Net Immunology & Vaccine Protection Pillar Co-Lead Dr. Jen Gommerman is helping to pilot.
“Based on animal data, mucosal nasal boosters have been shown to protect against infection in addition to severe disease. Because the immune system found in the nose and throat produces antibodies that are physically more flexible, we have reason to believe that nasal boosters may stimulate an immune response that is better able to cope with diverse variants,” says Dr. Gommerman, also Canada Research Chair in Tissue Specific Immunity and Professor at University of Toronto.
“Ultimately, we hope to combine these approaches, developing a pan-variant or a pan-coronavirus nasal spray that offers broad and durable protection against new SARS-CoV-2 variants and related coronaviruses,” says Dr. Gommerman.
Answer from the experts: Get the booster that’s available to you
Will it be a few weeks, a month or longer until bivalents tailored to BA.5 are approved and available to you and your family here in Canada? It’s still not clear, especially when we consider all age groups.
“What is clear is that BA.5 remains prevalent in communities across Canada, and the immune protection against infection is dropping, particularly in individuals who were vaccinated and/or infected early in the Omicron wave,” says Dr. Otto. “Modelling this declining immunity suggests that the next wave will start this month or next, even without a more transmissible variant, but we can keep this next wave small if many Canadians choose to get boosted.”
“We don’t know what will happen in the fall as far as the 8th COVID-19 wave or when bivalents tailored to BA.4 and BA.5 will be approved and available to Canadians. If your last dose was many months ago and you were not recently infected, it makes sense to get the booster that’s available,” says Dr. Gommerman.
NACI recommends waiting three months after an infection before getting another shot, and three to six months between doses, but also said in its most recent guidance that anyone at high risk of severe COVID in Canada should be offered a fall booster.