A single yearly injection that protects against influenza, COVID-19 and respiratory syncytial virus (RSV) could one day simplify seasonal vaccination and save lives, according to new research from the University at Buffalo, although scientists caution that the experimental vaccine still has to prove itself in human trials.

The findings, published in Science Advances, come as doctors continue to grapple with the post-pandemic "tripledemic"—the seasonal overlap of flu, COVID-19 and RSV that has strained hospitals since 2022. During the 2023-24 respiratory virus season alone, the three infections were linked to about one million hospitalisations in the United States, underscoring the burden these viruses place on healthcare systems.

Researchers tested the vaccine in mice, ferrets and cotton rats—animal models widely used because they develop respiratory infections in ways that resemble humans. The single formulation generated protective immune responses against all three viruses without one component appearing to weaken another, a problem scientists call "immune interference".

"The antibody responses were comparable to those produced by vaccines that target just a single virus, suggesting that combining the three vaccines into one shot did not weaken their effectiveness," said Jonathan Lovell, corresponding author of the study and SUNY Empire Innovation Professor in the University at Buffalo's Department of Biomedical Engineering.

Instead of using messenger RNA (mRNA), the technology behind many COVID-19 vaccines, the experimental vaccine uses harmless viral proteins attached to microscopic cobalt-based nanoparticles. These tiny particles help train the immune system to recognise and fight viruses. The platform, known as CoPoP, has been under development for more than a decade and has already supported a COVID-19 vaccine candidate that advanced to Phase 2 and Phase 3 clinical trials in South Korea and the Philippines.

Scientists say convenience may be as important as science. Despite recommendations, vaccination rates remain modest. As of November 2024, only 35% of Americans aged 75 years and older had received a flu vaccine, 18% had received a COVID-19 vaccine and 40% an RSV vaccine.

"We know that many people skip one or more of the three recommended respiratory vaccines, sometimes simply because it's inconvenient," said co-author Bruce Davidson. "Replacing them with one annual shot could lower the barrier and vastly improve immunisation rates," Davidson said.

The study, supported by the US National Institutes of Health and a McGill University grant, adds to growing global efforts to develop combination vaccines. However, the researchers stress that larger studies and human clinical trials are essential before such a vaccine could become part of routine healthcare. If successful, one injection could eventually make seasonal protection simpler, broader and easier to accept.