Impact of Maternal Antibodies and Weaning Stress on the Replication and Transmission of Human H3N2 Influenza A in Piglets

Abstract

Modern swine production facilitates indoor respiratory contact between human employees and pigs in their care, creating conditions for interspecies transmission of influenza A virus (IAV). Sow vaccination is routinely practiced in the U.S. to transfer maternal derived antibodies (MDA) to piglets. Weaning is a highly stressful period for piglets that requires increased human interaction. This study investigates the effect of maternal antibodies on the susceptibility of weaned piglets to a human-origin H3N2 IAV. Weaned piglets often possess mixed immunity from MDA, which may be antigenically matched or mismatched to circulating viruses. Given the repeated spillover of human seasonal H3N2 into swine, we specifically examined how matched and mismatched MDA, acquired from vaccinated sows, influenced piglet susceptibility. Additionally, we assessed the impact of weaning-related stress on the outcome of viral challenge. The H3N2 virus was generated by reverse genetics to mimic the 2010.1 H3N2 introduction from humans to swine. Challenged seeder piglets were divided by immune and weaning status. Two days post inoculation, naive direct contact pigs were placed with seeders. IAV qRT-PCR and virus titration were performed on nasal swabs and bronchoalveolar lavage fluid to evaluate shedding and transmission kinetics. Matched MDA were effective in reducing shedding in challenged pigs and minimizing transmission to contacts. There was an increase in shedding and transmission in weaned pigs compared to littermates that remained on the sow. These results identify critical control points in production where changing practices could mitigate human-to-swine and swine-to-swine transmission to prevent 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.