Concern about pandemic influenza looms as H5N1 viruses spread across species and continents. Although human cases remain limited, the current US outbreak raises alarming questions about preparedness for a pandemic. At this critical juncture, decisions about vaccine development, stockpiling, and deployment will shape the ability to respond to immediate and future pandemic risks.

North America is increasingly impacted by H5N1 influenza infections among poultry, cows, wild birds, and marine and terrestrial mammals, including at least 13 human infections related to animal contact,¹ with genetic clade 2.3.4.4b viruses responsible for most recent cases. Although human illness has been mild so far, previous H5N1 viruses caused substantial mortality. Additionally, human-to-human transmission has not been reported in this outbreak and was uncommon with prior H5N1 strains, but surveillance is limited. The current extent of mammalian infection appears unprecedented, and a 2024 study suggested the virus may have acquired enhanced ability to bind mammalian airway receptors.² The widespread presence of H5N1 among animals in proximity to humans, despite biocontainment efforts, increases risks for reassortment between human and animal viruses and selection of mutations that could enhance human transmission and threaten a pandemic.