A caprine mammary infection model for highly pathogenic avian influenza H5N1

Highly pathogenic avian influenza (HPAI) H5N1 virus spillover into dairy cows represents the emergence of a mammalian host capable of sustaining a panzootic and creates a transmission pathway to humans. HPAI research involving dairy cows is constrained by the space requirements needed to house large animals in high biocontainment. A small ruminant model would enable larger sample sizes while reducing costs, improving safety, and lowering logistical barriers to conduct research. Here, we establish dairy goats as a model for HPAI mammary infection. Intramammary inoculation with HPAI H5N1 genotype D1.1 and genotype B3.13 resulted in acute mastitis, decreased milk yield, and high virus shedding in milk. Parenteral vaccination with an inactivated virus induced antigen-specific antibodies in blood and milk, reduced clinical disease, limited virus shedding in milk, and mitigated milk production losses. HPAI H5N1 disease dynamics in dairy cows can be recapitulated in dairy goats, providing a relevant model for investigating pathogenesis and for supporting the development of control strategies.