Is a ‘super-seasonal’ flu vaccine on the horizon? The NIH and UW are taking a shot into the clinic this April

Several biotechs and pharma companies are looking to discover a universal flu vaccine that could protect humans from any strain of the virus, regardless of which is predicted to circulate. But given how many of these efforts are likely years away at best, are there any intermediate steps available to bridge that gap?

That’s the question University of Washington researcher Neil King and a group of NIH scientists are hoping to answer. In a new Nature paper published Wednesday, the team was able to demonstrate broad effectiveness in animal models for a “super-seasonal” flu vaccine by displaying multiple flu strains at the same time. And King says it’s starting human trials at the end of April.

The big idea is instead of getting different flu shots every year as the virus mutates, one could get protection from one vaccine for three to five years, King said.

“Even that would be a massive advance,” King told Endpoints News. “The virus mutates a little bit and you’re still covered. And the next year it mutates a little bit more and you’re still covered.”

The technology King used to accomplish this is similar to virus-like particles, though he says he would not use that term for “very technical reasons.” It’s still used in a similar fashion, however, only instead of utilizing a capsid that lacks a genome, the group designed protein nanoparticles that can self-assemble.

Essentially what you get are two of these nanoparticles, which separately don’t do much. But when you mix them together in a test tube, King said, they assemble themselves into a new molecule that can function like a VLP. The technology is the same that’s being used by Icosavax, though the company was not involved in this specific paper.

Super-seasonal flu shots have been attempted before, but the underlying twist here is while the in vitro assembly of the nanoparticles was the same, King and the NIH team managed to codisplay multiple flu strains on the same nanoparticle. They managed to induce broad responses in mice, ferrets and non-human primates, hitting not just the “head” of the specific strains but also the “stem.”

The stem of the virus strain — whose scientific jargon name is hemagglutinin — is what many scientists have been after for a universal flu shot, King said, as current flu shots only go for the head. Some approaches involve cutting off the head to focus only on the stem, but the nanoparticle approach managed to train the immune system to attack both.

“Traditionally that’s been very hard. The immune system just doesn’t react very strongly to the stem,” King said. “But something about putting these hemagglutinins on our nanoparticles taught the immune system, ‘Hey, give me the head … but also go get that stem too.’ And that is what’s providing the protective breadth from these vaccines.”

On top of that, the group used the same strains currently in commercial flu shots. That proved a key part in their efforts, King said, because it makes a potential regulatory path through the FDA much easier.

Because their experimental vaccine has already been manufactured, the NIH is barreling ahead with a Phase I trial planned to start next month. By the end of the year, King says the nanoparticle technology will have four vaccine programs in the clinic: the super-seasonal flu shot, two potential Covid-19 vaccines and a program for respiratory syncytial virus, or RSV.

But in order to fully commercialize the flu shots and take them all the way through pivotal Phase III studies, King said they still need a pharma company to license the program. There has been initial interest from at least two companies, though King stayed mum on who’s looking.

At the end of the day, the super-seasonal flu shots are still a ways away from their first sales and even longer from replacing conventional flu vaccines, which still use technology from the 1930s by growing the predicted strains inside chicken eggs, King said. A traditional timeline pre-Covid-19 might have taken 10 years, but now everything is up in the air.

“After what we saw in 2020 with SARS-CoV-2, I don’t know,” King said about a timeline. “It could be faster. But this thing is entering Phase I next month, you have to do Phase II, Phase III, these things do take time. So my guess is it would be at least five years, but who really knows?”