A universal flu vaccine – one that would protect against multiple strains and could spell the end of yearly shots – is something virologists have been striving towards for a long time. Now, one candidate has moved a step closer to fruition, showing positive results in ferrets. Researchers hope to begin human trials in as little as one to three years.

Developing each season’s new flu shot is something of a guessing game. Scientists can use data from previous years, tracking which different strains of the virus are dominating. They can also watch for trends on the opposite side of the planet since the Southern Hemisphere’s flu season draws to a close just as the Northern Hemisphere’s is kicking off. So, it’s a highly data-driven guessing game, but it still doesn’t always produce perfect results. 

The real breakthrough would be the development of a vaccine that works against multiple different flu strains. That way, we’d have a much better chance of coverage against all the flu strains that circulate within a season, as well as providing protection that would last for more than just one year – and there’s a chance of building our defenses against any sneaky pandemic strains that might come along into the bargain.

Numerous groups are working towards this goal, and there have been promising results in recent years for several vaccine candidates. The latest news comes from a team at the Cleveland Clinic’s Lerner Research Institute, who have been testing their universal vaccine in ferrets.

The vaccine was developed using a method called COBRA (Computationally Optimized Broadly Reactive Antigens). Thousands of genetic sequences from influenza viruses that cause human diseases, covering years of flu seasons, were analyzed to look for amino acid signatures that were conserved between them. Eight proteins were pulled out for inclusion in the vaccine.

“We’ve been able to whittle down this list, to say these are the best at spanning multiple seasons and eliciting a broadly reactive antibody response,” explained study lead and virologist Dr Naoko Uno in a statement. “It’s like creating a greatest hits album. We want to put only the best ones back in the vaccine.”

The proteins appear in a range of influenza A strains in the H1, H2, H3, H5, and H7 groups, as well as influenza B. When naming flu viruses, the H refers to the surface protein hemagglutinin. It’s coupled with an N, short for neuraminidase, and these two proteins together categorize the virus. You might remember the H1N1 swine flu pandemic, for example, or have heard references to H5N1 bird flu in the media recently.

H5N1 is a particular worry at the moment, as it’s been seen to spread to a range of mammal species as well as circulating in wild and farmed birds. Dairy farms in 13 US states have been hit with outbreaks, resulting in four confirmed cases in farm workers to date. Seasonal flu is always a threat to health, but the specter of a future pandemic underlines even more why broadly protective vaccines are so needed. 

With their eight proteins identified, the team tested the vaccine by administering it to ferrets through their noses. They're a great model for influenza research as they're susceptible to human viruses (which also means you should take care around your pet ferret if you catch the flu!) Four weeks later, tests confirmed that the ferrets had developed antibodies against influenza, and when they were then exposed to the virus, they did not get sick.

This follows earlier, similarly positive results in mice from the same group of researchers. The hope is that they can now progress to clinical trials in humans in one to three years. “We want to make sure our vaccine can span multiple seasons, not just one, and protect against all the strains that affect humans,” Uno said. 

And the good news doesn’t end there. The COBRA method could be applied to other viruses too, and might give us a new way to develop vaccines against diseases like dengue. 

Not bad for eight little proteins. 

The study is published in the Journal of Virology.