High serological barriers may contribute to restricted Influenza-A-virus transmission between pigs and humans.

Influenza A viruses (IAV) circulate in both humans and pigs, with bidirectional transmission potentially driving viral evolution. Despite frequent contact and genetic compatibility, observed cross-species transmission remains rare, suggesting the presence of unexplored or little-known barriers. The study investigated transmission dynamics and mechanisms restricting IAV spread at the human-swine interface in Germany. We analyzed 3070 porcine and 333 human nasal swabs from 135 swine farms via RT-qPCR and full-genome sequencing. Concurrently, we conducted serological surveys: 1) Children's sera (urban, no pig contact) for antibodies against circulating swine IAV, and 2) Swine sera for antibodies against human-adapted IAV. Molecular surveillance identified only one zooanthroponosis event and sporadic anthropozoonosis (primarily in children) despite swine IAV strains carrying zoonotic-propensity genetic markers (MxA resistance). Serologically, urban children without pig exposure exhibited marked neutralizing activity against swine IAV, whereas swine sera contained neutralizing antibodies against human IAV strains. Pre-existing cross-reactive immunity-evidenced by unexpected antibody prevalence in both species-creates a more complex interspecies barrier than genetic factors alone. This serological "shield" may critically limit IAV transmission between humans and pigs, reshaping our understanding of zoonotic risk.