Experimental vaccines targeting more stable parts of influenza viruses have produced encouraging immune responses, but protection across flu strains remains a research goal.
Scientists are developing influenza vaccines that could provide broader and longer-lasting protection than conventional seasonal shots. One approach, investigated by researchers at the US National Institutes of Health (NIH), targets the relatively stable stem of hemagglutinin, a protein on the virus’s surface. Its exposed head changes more frequently, helping influenza evade existing immune responses.
These gradual changes, known as antigenic drift, are a major reason people can catch influenza repeatedly. They also explain why the composition of seasonal flu vaccines is reviewed annually and updated when necessary to better match circulating viruses.
Early clinical results suggest that targeting the stem can broaden the immune response. A 2023 phase 1 study involving 52 healthy adults, published in Science Translational Medicine, tested an experimental nanoparticle vaccine called H1ssF. It generated antibodies capable of neutralising multiple group 1 influenza viruses in laboratory tests, with responses observed more than a year after vaccination. The vaccine was generally well tolerated in this small study.
Those findings require careful interpretation. The trial primarily assessed safety and antibody responses; it did not establish protection against every influenza strain or demonstrate that annual vaccination could be replaced. Most participants were scheduled to receive two doses, so the results also do not support claims of universal protection from a single injection.
Researchers are exploring several ways to deliver these broader targets. In May 2023, NIH announced a separate phase 1 trial of H1ssF-3928 mRNA-LNP, an mRNA-based candidate targeting the hemagglutinin stem. That announcement described a safety and immune-response study, rather than evidence of clinical effectiveness.
If successful, broadly protective vaccines could reduce reliance on frequent reformulation and strengthen preparedness for unexpected influenza variants. Establishing that benefit will require larger trials measuring actual infections and severe illness, alongside longer follow-up to determine how well protection lasts.
Sources:
CDC — How influenza viruses change through drift and shift
Clinical study — H1ssF vaccine responses in healthy adults
NIH — Trial of an mRNA universal influenza vaccine candidate
