Pathogenesis and transmission assessment of three swine-origin influenza A(H3N2) viruses with zoonotic risk to humans isolated in the U.S from 2017-2020.

The sporadic occurrence of human infections with swine-origin influenza A(H3N2) viruses and the continual emergence of novel A(H3N2) viruses in swine herds underscore the necessity for ongoing assessment of the pandemic risk posed by these viruses. Here, we selected three recent novel swine-origin A(H3N2) viruses isolated between 2017 to 2020, bearing HAs from the 1990.1, 2010.1 or 2010.2 clades, and evaluated their ability to cause disease and transmit in a ferret model. We conclude that despite considerable genetic variances, all three contemporary swine-origin A(H3N2) viruses displayed a capacity for robust replication in the ferret respiratory tract and were also capable of limited airborne transmission. These findings highlight the continued public health risk of swine-origin A(H3N2) strains, especially in human populations with low cross-reactive immunity.