Bovine Derived Clade 2.3.4.4b HPAI H5N1 Virus Causes Mild Disease and Limited Transmission in Pigs

Highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b emerged in dairy cows in the United States in early 2024. Since then, this clade simultaneously circulates in wild birds, cattle and poultry with ongoing transmission into several mammalian species. Given the historical role of swine in influenza ecology, susceptibility of pigs to this virus is critical for animal and public health. To address this concern, Sinclair nanopigs were infected with a bovine clade 2.3.4.4b HPAIV H5N1 isolate by combined intranasal, intratracheal and oral administration mimicking possible natural exposure routes. Pigs were productively infected developing either subclinical or mild disease with seroconversion. Virus replication occurred mainly in respiratory tissues resulting in shedding from upper respiratory tract mucosae. Limited transmission to naïve contact cage mates was documented in a subset of transmission pairs. The combination of subclinical clade 2.3.4.4b HPAIV H5N1 replication and limited transmission draws an alarming scenario for One Health considering pigs are a favorable influenza mixing vessel enabling mammalian adaptation.