New mRNA vaccine targeting all known strains of influenza shows early promise

A new mRNA vaccine that targets all known strains of influenza in a single injection is showing promise in animal studies and opening the door to a multitude of possibilities with vaccine technology — including potentially preventing the next influenza pandemic.

University of Pennsylvania researchers published their results in the journal Science Thursday, which showed the vaccine elicited high levels of antibody protection in mice and ferrets against all strains of influenza, which could one day help pave the way for a universal influenza vaccine.

The research is rapidly taking mRNA technology to new heights, building on the advances made during the COVID-19 pandemic to accelerate the development of the new vaccine platform that has already been used effectively by billions of people worldwide.

“Our approach was to create a vaccine that encodes every influenza subtype and lineage that we know of,” said Scott Hensley, an immunologist at the University of Pennsylvania in Philadelphia and one of the study’s lead authors.

“The goal was to establish a baseline level of immune memory that can be recalled when a new strain of the pandemic emerges.”

Unlike seasonal flu shots, which protect against existing circulating strains each year but offer little protection against strains that can spread from animals and cause pandemics, such as H1N1 in 2009this vaccine could theoretically provide immunity to all new strains of influenza.

“We are still in pre-clinical testing at this stage, we are planning a phase 1 human trial, but so far from animal models it looks like this vaccine has achieved our goal of broadly inducing immune memory,” said Hensley.

“Imagine if the population were prepared with this vaccine, we might not necessarily see protection against infection with new strains of the pandemic, but rather a reduction in hospitalizations and serious illnesses – and that’s really our main goal.”

While a potential vaccine could be years away pending successful human testing, the development of a flu shot that can target all 20 known influenza A and B strains is an amazing 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-authored an independent study Perspectives on the study of natural sciences.

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

A registered nurse delivers a Pfizer COVID-19 vaccine to a frontline worker at Vancouver General Hospital in Vancouver, March 2021. The mRNA technology used in COVID vaccines has significant potential for other forms of disease. (Ben Nelms/CBC)

‘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 worldwide every year – if clinical trials and regulatory approvals pass.

“This is a way to cover a huge family of viruses that cause a huge burden of disease around the world every year,” Kelvin said. “In addition, there is a constant risk that a new influenza virus will spill over. So it could cover not only what we’re currently looking at, but also what we don’t know.”

There are still important unanswered questions about researching and developing 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 would say completely through the door – of clinical application,” said Gary Kobinger, director of the Galveston National Laboratory at the University of Texas who helped develop a Canada-led Ebola vaccine.

“It’s one of those times when you see scientific work done in animals and you know that in a short to medium term time frame it could be the case in humans,” he added. “Let’s see if that works. We all hope it works.”

The vaccine used lipid nanoparticlesa successful mRNA vaccine delivery system developed by Canadian scientist Pieter Cullis and researchers from the University of British Columbia to target all known strains of influenza that are constantly circulating and infecting us every year.

CLOCK | Harnessing the potential of mRNA vaccines:

The possibilities of mRNA vaccines beyond COVID-19

The breakthrough technology used to make Pfizer and Moderna’s COVID-19 vaccines, mRNA, could also be used to make vaccines for other diseases like HIV, flu and even cancer.

“The vaccine induces broad immunity in mice and ferrets that have never seen the virus before. It mimics how this vaccine might work in young children,” Hensley said.

“But we found that the vaccine can also produce these broad responses in animals that have had and recovered from influenza.”

That means if the vaccine were proven safe and effective in humans and successfully approved, it wouldn’t just be limited to children who have never had the flu before. It could also be used more widely in the general population — including the elderly, who are often at higher risk for serious complications.

“I think we can expect vaccine developers to go in all sorts of directions,” Kelvin said. “I can’t predict what that will be, but the sky is the limit as to what will be done in the next few years.”

Hensley said the researchers weren’t sure the platform would even work in animals because of potential problems with what’s known as immune dominance hierarchies — where our immune systems respond to certain strains more efficiently than others.

“We didn’t find that, we found that this vaccine elicited antibodies in fairly equal amounts against all antigens encoded,” he said. “So that was an important finding.”

The fact that strong antibody immune responses were shown against all 20 different strains of influenza is very encouraging, Kelvin said, because even if the strains aren’t all circulating at the same time, there’s a possibility that influenza strains could spread from animals drive a pandemic at any time.

“We know that there will be another spillover of an influenza virus with pandemic potential,” she said. “Are we keeping this vaccine on the shelf ready for use? Or do we want to consider licensing for more seasonal approaches?”

However, there are major regulatory hurdles to getting such a complex and far-reaching vaccine approved — even if it passes clinical trials.

“The biggest question is how do we get that into people? Because what’s engineered into the vaccine are targets for viruses that aren’t currently circulating in humans,” Kelvin said.

“So when regulators look at how they’re evaluating a vaccine and approving it for human use, they want to make sure it’s safe and effective. Now what is the efficacy we are going to say for this vaccine ?”

And while traditional flu vaccines are already effective in preventing serious illness and death in those most at risk when successfully matched with circulating strains, widespread uptake of the flu shot remains a major challenge.

CLOCK | Flu and an overburdened healthcare system:

Concerns are growing about the triple threat of rising respiratory diseases

The Ontario Medical Association is urging people to wear masks indoors and get vaccinated against the flu and COVID-19 amid growing concerns that a surge in flu cases could overwhelm a healthcare system that is already handling an influx of RSV and COVID patients recorded.

According to the latest study, less than 40 percent of Canadians chose to get a flu shot in 2020 federal data, although it is recommended and available for anyone older than six months. In the US, that number is slightly higher more than 50 percent.

And only one in five Canadians has received a COVID booster or completed a first vaccination course in the last six monthswhile just over 10 percent of Americans have opted for a bivalent booster dose targeting the dominant circulating subvariant Omicron BA.5.

“That’s the reality,” said Kobinger. “You can have the best vaccine in the world, but if nobody wants it or takes it, it’s useless.”