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A ‘universal’ vaccine, that broadly protects against all influenza A viruses (IAVs), is urgently needed. Park et al. now demonstrate that intramuscular or intranasal delivery of an inactivated multivalent IAV vaccine cocktail (composed of four β-propiolactone–inactivated low pathogenicity avian IAV subtypes of H1N9, H3N8, H5N1, and H7N3) protects against multiple IAV hemagglutinin and neuraminidase subtypes in both mice and ferrets, including antigenically variable and heterosubtypic avian, swine, and human viruses. Vaccinated animals displayed reduced viral titres, lung pathology and inflammatory responses, without any signs of toxicity. A phase I safety and immunogenicity study of the vaccine has been initiated.