Increased contact transmission of contemporary Human H5N1 compared to Bovine and Mountain Lion H5N1 in a hamster model.

The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the U.S. poses a significant public health threat. To date, 70 human cases have been confirmed in the United States, including two severe cases and one fatality. While suitable animal models are crucial for predicting the potential pandemic risk of newly emerging pathogens in humans, studies investigating contemporary HPAIV H5N1 transmission dynamics remain limited. Here, we investigate the pathogenicity and transmission efficiency of recent clade 2.3.4.4b H5N1 viruses isolated from a bovine, mountain lion, and a human case using Syrian hamsters. Intranasal inoculation results in productive virus replication in the respiratory tract and shedding for all three isolates. Transmission studies demonstrate limited efficiency via direct contact and airborne routes for all isolates. Although overall transmission is inefficient, the human H5N1 isolate demonstrates relatively greater contact transmissibility than the bovine and mountain lion isolates. Taken together, our findings demonstrate that the Syrian hamster model complements existing animal models for influenza A virus research and expands the resources available for investigating the pathogenicity, transmissibility, and efficacy of countermeasures against HPAIV H5N1.