Association of poultry vaccination with the interspecies transmission and molecular evolution of H5 subtype avian influenza virus

The effectiveness of vaccinating poultry in preventing the transmission of highly pathogenic avian influenza viruses (AIVs) has been questioned for years and its impact on wild birds is uncertain (1-3). Here we reconstruct movements of H5 subtype AIV lineages among vaccinated poultry, unvaccinated poultry, and wild birds, worldwide from 1996 to 2023. We find that lineage transitions among host types are lagged and that movements from wild birds to unvaccinated poultry were more frequent than those from wild birds to vaccinated poultry. However, we also find that the HA gene of the AIV lineage that circulated predominately among Chinese poultry with high vaccination coverage underwent faster evolution and greater nonsynonymous divergence than other lineages. Further, this Chinese poultry lineage contained more codons inferred to be under positive selection, including at known antigenic sites, and its rates of nonsynonymous divergence and adaptative fixation increased after mass poultry vaccination began. Our results indicate that the epidemiological, ecological and evolutionary consequences of widespread AIV vaccination in poultry may be linked in complex ways, and that much work is needed to better understand how such interventions may affect AIV transmission to, within and from wild birds. ### Competing Interest Statement The authors have declared no competing interest.