One shot to rule them all in the fight against H5 influenza

The immunological arms race between virus and vaccines may change in the future, at least for bird flu viruses. Scientists have developed a proof-of-concept vaccine against avian influenza viruses that offers protection against all the variants, including those that are yet to evolve (Nature 2025, DOI: 10.1038/s41586-025-09626-3).Influenza A viruses are categorized into different subtypes according to a surface glycoprotein called hemagglutinin. The H5 subtype can evolve into highly pathogenic avian influenza viruses (HPAIVs) that devastate flocks of poultry and wild birds around the world. A lineage of bird flu has spread globally since it was first detected in Hong Kong in 1997. Variants of this virus have caused catastrophic outbreaks in marine mammals and US dairy cows; the continuous churning out of newer genetic and antigenic variants ensures that vaccines are always trying to catch up. Mathilde Richard of Erasmus University Medical Center and her team decided to develop a master antigen that could immunize against all known H5 viruses. First, they used 14,896 nucleotide sequences collected from all known variants of H5 influenza to create an evolutionary tree of H5 the virus . They then used these sequences to create a high-resolution, 3D map showing the antigenic evolution of H5 influenza since 1959.By focusing on 12 wild-type antigens at the map’s center, the researchers designed candidate vaccine antigens that could bind bird cells as well as human cells. They eventually settled on one called AC-Anhui.To test its efficacy and breadth, the researchers vaccinated some ferrets with a vaccine prepared