Comparative Evaluation of Pathogenesis and Airborne Virus Shedding in Ferrets Infected with Diverse Influenza Virus Strains

Recent A(H5N1) zoonotic cases linked to poultry and cattle in North America highlight the urgent need to assess the pandemic potential of emerging strains. Using the ferret model, we evaluated two B3.13 and two D1.1 genotype A(H5N1) viruses isolated from humans. All viruses caused rapidly progressing disease with high mortality and showed varying capacities for direct contact transmission. To improve pandemic risk assessment, we conducted aerosol sampling with two air collection platforms and expanded our analyses to include additional A(H5N1), A(H9N2), A(H7N9), and A(H1N1)pdm09 strains with known transmissibility profiles. Although none of the A(H5N1) strains transmitted via the air, B3.13 viruses were detected at significantly higher levels compared to D1.1 strains. We found strong correlations between viral loads in nasal washes, airborne virus shedding, and transmissibility potential, highlighting the value of these metrics for identifying zoonotic influenza viruses that may be adapting toward mammalian transmissibility, even without detectable airborne spread.