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For decades, the flu virus in the shots you’re offered every fall has been grown in chicken eggs.
While that may sound odd, the tried-and-true technology has been around since the 1940s. Now, scientists are trying more modern methods of developing vaccines.
It’s not a diss against the millions of hens and their eggs that go into making influenza vaccines for the world every year, because the system does work, experts say. But supplies can run short, and eggs can cause problems that researchers are making progress on solving.
Twice a year, the World Health Organization convenes an expert panel to decide what should go into vaccines for the coming flu season in each hemisphere, based on the highest-circulating strains. It takes six months to decide which strains to include, purify the seed ingredients, mass produce the shots in eggs and get them into vials to go into arms.
The steps add up to a sluggish ability of vaccine makers to adapt to the fast-evolving virus, meaning last year’s vaccine may not protect against this year’s strain. And the respiratory disease is highly contagious, in most cases causing fever, coughing and body aches, but potentially leading to severe complications like pneumonia.
Another part of the problem is that many flu viruses originated in birds, virologists say.
“You’re growing it in embryonated chicken eggs,” said Dr. Lynora Saxinger, an infectious diseases specialist at the University of Alberta in Edmonton. “And so that’s avian cells that are growing the virus for you and the virus actually adapts to grow better in the avian cells.”
That can sometimes result in viruses that look less like what’s causing infections in humans, which can further decrease the effectiveness of influenza vaccines, said Matthew Miller, director of the Degroote Institute for Infectious Disease Research at McMaster University in Hamilton, Ont.
Proof-of-concept vaccine
Last week, the New England Journal of Medicine published Phase 3 of a clinical trial pointing to a potentially more effective option: mRNA flu shots.
Pfizer scientists tested a flu shot made with the same mRNA technology used in COVID-19 vaccines against a traditional egg-based flu vaccine in more than 18,000 adults in the U.S., South Africa and the Philippines during the 2022–23 flu season. They found the mRNA version offered 34 per cent more efficacy. There was no placebo comparison.
“That actually is a significant increment of better protection in a single season with the strains that were circulating with this product,” Saxinger said. “It’s an important proof of concept that is worth pursuing.”
In the study, mild to moderate side effects like fever, chills and redness were more common among those who received an mRNA influenza vaccine than the traditional jab.
“Twenty-four hours of feeling lousy seems to be a feature of current mRNA [vaccines],” Miller said. “I think there are ways that the mRNA [vaccine technology] can evolve in the future to alleviate some of those systemic effects.”
Overall, for a single study, the take-home message is encouraging, said Angela Rasmussen, principal research scientist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan.
U.S. Health Secretary Robert F. Kennedy Jr., a longtime vaccine critic, claimed this week that mRNA vaccines can prolong pandemics. Angela Rasmussen, a virologist at the University of Saskatchewan, explains why mRNA vaccines actually help to shorten pandemics.
But disinformation about mRNA vaccines remains a problem. Rasmussen, who was recruited to Canada in 2021 from Columbia University in the U.S., is an active public communicator of vaccine science.
“It’s really important that we meet people where they are; we address their concerns and their questions,” Rasmussen said.
“But we also really can’t tolerate having people interject things that aren’t true about these vaccine platforms as an argument to avoid developing them further.”
Weighing speed and cost
In traditional egg-based vaccines, the virus is grown in the eggs and inactivated with a chemical. That way, just the virus particles remain for a person’s immune system to recognize without the virus being able to replicate itself and cause infection, Rasmussen said.
In cell-based flu vaccines, including one product available in Canada, the virus is grown in the cells of dog kidneys instead of chicken eggs.
That means avoiding the issues that come with having the virus grow in bird eggs.
Another plus is cell vaccines can be manufactured faster, Miller said.
“In theory, the [World Health Organization], for example, could provide a later recommendation that’s closer to the flu season that avoids the probability of mismatch happening.”
A disadvantage is that the cell-based vaccine is significantly more expensive, said Dr. Barry Pakes, an associate professor at the University of Toronto who treats respiratory infections including influenza.
Pakes said that while vaccines are simple to protect someone, producing them is complex and resource-intensive. More Canadian manufacturing of vaccines could help secure supply.
“Onshoring some of that — certainly with the political climate in the U.S. — is really important,” Pakes said.
Multi-season protection?
Another non-egg based influenza vaccine technology is a lab-made or recombinant version that is also faster to produce.
In Canada, there’s one version of this available for influenza, according to Miller. It has a purified part of the virus called hemagglutinin, made in insect cells.
Choice is helpful to see the benefits and drawbacks of various vaccine platforms, he said.
“There’s lots of renewed efforts to develop better mucosal vaccines either administered as a nasal spray or administered by aerosol, which is what our group does,” Miller said.
That McMaster vaccine is still at the pre-clinical stage of research, meaning it hasn’t been tested in humans.
“We are developing aerosolized influenza vaccines that we hope will provide better protection against both seasonal and pandemic viruses that’s not only stronger but also longer lasting, multi-season protection.”
For the foreseeable future, Canada’s flu vaccine supply will likely continue to be mainly egg-based, Pakes and Miller said.
“Egg-based vaccines have done a good job for a long time,” Miller said. “The comparative data suggests … they do a very good job preventing severe illness.”
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