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

Authors: CIACCI ZANELLA, GIOVANA - Iowa State University; CARDENAS, MATIAS - University Of Georgia; HUTTER, CARL - Oak Ridge Institute For Science And Education (ORISE); SNYDER, CELESTE - Iowa State University; Wymore Brand, Meghan; Arruda, Bailey; PEREZ, DANIEL - University Of Georgia; Anderson, Tavis; RAJAO, DANIELA - University Of Georgia; Baker, Amy

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/18/2026
Publication Date: 3/27/2026
Citation: Ciacci Zanella, G., Cardenas, M.I., Hutter, C.R., Snyder, C.A., Wymore Brand, M.J., Arruda, B.L., Perez, D.R., Anderson, T.K., Rajao, D.S., Baker, A.L. 2026. Impact of maternal antibodies and weaning stress on the replication and transmission of human H3N2 influenza A in piglets. Journal of Virology. https://doi.org/10.1128/jvi.01975-25.
DOI: https://doi.org/10.1128/jvi.01975-25

Interpretive Summary: Both humans and pigs are natural hosts of influenza A viruses and share close contact in commercial pig farms, which creates opportunities for flu viruses to spread between both host species. Piglets are not born with antibodies; they must ingest colostrum from their mothers quickly after birth to create maternally derived immunity. To control influenza in the field, swine producers and veterinarians vaccinate the pregnant sows with influenza A vaccines so that they can transfer antibodies to their piglets. However, these vaccines are not always appropriately chosen and don't protect the piglets against newly introduced viruses. In addition, a critical moment for young piglets is weaning, when they are separated from their mothers. Weaning is stressful and involves more handling from human employees; this process also often mixes piglets with different immunological backgrounds and exposes them to new influenza A viruses. Our study tested how different maternal immunity statuses and weaning stress affect a piglet's ability to become infected with and transmit human influenza to other piglets. We found that piglets who received fully protective antibodies from their mothers shed very little to no virus to their contacts, and that piglets that received partially protective antibodies shed considerably less than those that received none. We also showed that weaning is stressful for the piglets, since weaned piglets had higher levels of circulating cortisol, the stress hormone, than the piglets that remained with their moms. And stress impacts how much virus a host sheds, since weaned piglets had higher levels of virus detected in their nasal swabs and for longer than those that stayed with their moms, especially in the groups with no and partially protective antibodies. Our results emphasize that swine producers and veterinarians must guarantee that sows provide proper immunity to their piglets and reduce piglets' exposure to human viruses during and after weaning to prevent human-origin flu viruses from being introduced and becoming established in pig farms.

Technical 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.A. to transfer maternal derived antibodies (MDA) to piglets. Weaning is a highly stressful period for piglets that requires increased human interaction. Weaned piglets potentially have mixed immunity from MDA: matched, mismatched, and naive. Since there have been multiple introductions of human seasonal H3N2 to swine, we assessed the effect of matched and mismatched MDA acquired from vaccinated sows and the stress of weaning on the susceptibility of piglets to a human-origin H3N2 IAV. 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, naïve 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 of the human-like H3N2 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.