Impact of maternal antibodies and weaning stress on the replication and transmission of human H3N2 influenza A in piglets.

Human seasonal H3N2 influenza A viruses (IAV) are repeatedly transmitted to swine. Modern indoor swine production facilitates close contact between human employees and pigs in their care during certain husbandry events, like weaning, that may increase the chance of interspecies transmission of IAV. This study investigated the effect of matched and mismatched maternal-derived antibodies (MDA) acquired from homologous and heterologous vaccinated sows on piglet susceptibility to a human-like H3N2 virus, generated to mimic the 2010.1-lineage H3N2 introduction from humans to swine. Additionally, we assessed the impact of weaning-related stress, along with immune status, on transmission to naïve direct-contact pigs. Seeder piglets from immune- and weaning-status groups were directly inoculated. Two days post-inoculation (DPI), naïve direct-contact pigs were placed with seeders. Nasal swabs were collected daily in seeder and contact pigs to evaluate shedding and transmission kinetics, and seeders were euthanized at 5 DPI to evaluate viral replication in the lower respiratory tract. Matched MDA was effective in reducing nasal shedding in challenged pigs and minimizing transmission to contacts, whereas mismatched MDA was not. Additionally, there was an increase in shedding and transmission in weaned pigs with mismatched MDA compared to littermates that remained on the sow. These results identify critical control points in swine production to implement practices for mitigating human-to-swine and swine-to-swine transmission to prevent the establishment of novel lineages in pig populations.IMPORTANCEDefining the factors that increase the susceptibility of pigs to infection with human influenza A viruses (IAV) is critical to understand why those viruses transmit to the new host. IAV is frequently detected in nursing pigs, where it was shown that maternal-derived antibodies (MDA) may reduce clinical signs but may not prevent infection and transmission. Infected weaned piglets can then move viruses from the sow farm to offsite nurseries, where they can cause outbreaks with clinical disease as MDA wanes. Determining management practices that can be modified to reduce interspecies transmission of viruses to pigs is economically beneficial to the swine industry and could help define measures to prevent new spillover events. Reducing spillover of human IAV into pig populations also benefits public health by reducing genomic and phenotypic diversity in swine and the subsequent potential for zoonotic transmission.