New mRNA vaccine targeting all known flu strains shows early promise

A new mRNA vaccine targeting all known flu strains in a single shot is showing early promise in animal studies and is opening the door to a wide range of possibilities with the vaccine technology including potentially preventing the next influenza pandemic.

University of Pennsylvania researchers published their findings in the journal Science Thursday, showing the vaccine produced high levels of antibody protection in mice and ferrets against all flu strains, which could one day help pave the way for a universal flu shot.

The research rapidly lifts mRNA technology to new heights and builds off the progress made in the COVID-19 pandemic in accelerating the development of the new vaccine platform, which has already been effectively used in billions of people worldwide.

"Our approach was to make a vaccine that encoded every influenza subtype and lineage that we know about," said Scott Hensley, an immunologist at the University of Pennsylvania in Philadelphia and one of the lead authors of the study.

"The goal was to establish a baseline level of immune memory that could then be recalled when a new pandemic strain emerges."

Unlike seasonal flu shots that protect against existing circulating strains each year but offer little protection against strains that can spill over from animals and spark pandemics, like H1N1 in 2009, this shot could theoretically provide immunity against all new flu strains.

"We're still in preclinical testing at this phase, we are planning a Phase 1 human study, but so far from animal models it does look like this vaccine achieved our goal of inducing immune memory in a broad way," Hensley said.

"Imagine if the population was primed with this vaccine, what we might see is not necessarily protection from infection with new pandemic strains but a reduction in hospitalizations and severe disease and that's really our main goal."

While a potential vaccine could be years away since it still needs to successfully undergo human trials, developing a flu shot that can target all 20 known influenza A and B strains is an astonishing scientific feat.

"It really shows that we can use mRNA vaccines in ways that we really hadn't thought of before," said Alyson Kelvin, a virologist at the University of Saskatchewan's Vaccine and Infectious Disease Organization who co-wrote an independent perspective on the study in Science.

"This is just the beginning of where we can take mRNA-based vaccines."

'Sky's the limit' with mRNA technology

The research opens up a world of new possibilities with mRNA vaccine technology.

And it also brings hope of one day preventing hundreds of thousands of hospitalizations and deaths from the flu globally each year if it passes clinical trials and regulatory approval.

"This is a way to cover a huge family of viruses that causes a large burden of disease each year around the world," Kelvin said. "As well, there's continual threats of a new influenza virus spilling over. So it could not only cover what we're currently dealing with, but what we don't know."

There are still key unanswered questions about the research and development of the vaccine to ensure it's safe and effective in clinical trials, Kelvin said, but the fact that animals were able to elicit strong and distinct immune responses to each strain is very promising.

"It really puts this strategy more than a foot in the door I'd say completely through the door of clinical application," said Gary Kobinger, the director of the Galveston National Laboratory at the University of Texas who helped develop a Canadian-led Ebola vaccine.

"It's one of those times where you see a scientific paper in animals and you know that this could be in humans in what would be a short-to-mid-term timeline," he added. "So let's see if this works. We all hope it will."

The vaccine uses lipid nanoparticles, a successful delivery system for mRNA vaccines developed by Canadian scientist Pieter Cullis and researchers at the University of British Columbia, to target all known flu strains that perpetually circulate and infect us each year.

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"The vaccine induces broad immunity in mice and ferrets who had never seen the virus before. That mimics how this vaccine might perform in young children," Hensley said.

"But we found that the vaccine can also induce these broad responses in animals who had already experienced and recovered from a flu infection."

That means if the vaccine were proven to be safe and effective in humans and successfully approved, it wouldn't just be limited in use among children who have never before had a flu infection. It could also be used widely in the general population including in seniors who are often at a higher risk of serious complications.

"I think we can expect to see vaccine developers going in all sorts of directions," Kelvin said. "I can't predict what those will be, but the sky's the limit of what will be done in the next couple of years."

Hensley said the researchers were unsure if the platform would even work in animals, given that potential issues can arise with what are called immunodominance hierarchies where our immune systems react to certain strains more efficiently than others.

"We didn't find that, we found that this vaccine elicited antibodies at fairly equal levels to all of the antigens encoded," he said. "So that was an important finding."

The fact that strong antibody immune responses were shown against all 20 different flu strains is very encouraging, Kelvin said, because even if the strains don't all circulate at once, there is potential for flu strains to spill over from animals and drive a pandemic at any time.

"We know that there will be another spillover of an influenza virus with pandemic potential," she said. "Do we keep this vaccine on the shelf ready to go? Or is this something that we want to consider licensing for more seasonal approaches?"

However, there are major regulatory hurdles in approving a vaccine this complex and wide-ranging even if it does pass clinical trials.

"The biggest question is, how do we get this into people? Because what's incorporated in the vaccine are targets for viruses that aren't currently circulating in people," Kelvin said.

"So when regulatory agencies look at how they're going to evaluate a vaccine and approve it in human use, they want to make sure that it's safe and effective. Well, what is the effectiveness that we're going to say for this vaccine?"

And while traditional flu vaccines are already effective at preventing severe illness and death in the most vulnerable when successfully matched against circulating strains widespread uptake of the flu shot remains a major challenge.

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The Ontario Medical Association is urging people to wear masks indoors and get their flu and COVID-19 shots as concern builds that a spike in flu cases could overwhelm a health-care system already seeing an influx of RSV and COVID patients.

Less than 40 per cent of Canadians opted to get a flu shot in 2020, according to the most recent federal data, despite being recommended and available for everyone older than six months old. In the U.S., that number is somewhat higher at more than 50 per cent.

And just one in five Canadians have gotten a COVID booster or completed an initial vaccine series in the last six months, while just over 10 per cent of Americans have opted for a bivalent booster dose targeting the dominant circulating Omicron BA.5 subvariant.

"This is the reality," Kobinger said. "You can have the best vaccine on the planet, but if nobody wants it or takes it then it's useless."