Swine-to-ferret transmission of antigenically drifted contemporary swine H3N2 influenza A virus is an indicator of zoonotic risk to humans

Authors: SOUZA, CARINE - Oak Ridge Institute For Science And Education (ORISE); Kimble, James - Brian; Anderson, Tavis; ARENDSEE, ZEBULUN - Oak Ridge Institute For Science And Education (ORISE); HUFNAGEL, DAVID - Oak Ridge Institute For Science And Education (ORISE); YOUNG, KATHARINE - Oak Ridge Institute For Science And Education (ORISE); GAUGER, PHILLIP - Iowa State University; LEWIS, NICOLA - Royal Veterinary College; DAVIS, C - Centers For Disease Control And Prevention (CDC) - United States; SHARMI, THOR - Centers For Disease Control And Prevention (CDC) - United States; Baker, Amy

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/23/2023
Publication Date: 1/24/2023
Citation: Souza, C.K., Kimble, J.B., Anderson, T.K., Arendsee, Z.W., Hufnagel, D.E., Young, K.M., Gauger, P.C., Lewis, N.S., Davis, C.T., Sharmi, T., Baker, A.L. 2023. Swine-to-ferret transmission of antigenically drifted contemporary swine H3N2 influenza A virus is an indicator of zoonotic risk to humans. Viruses. 15(2). Article 331. https://doi.org/10.3390/v15020331.
DOI: https://doi.org/10.3390/v15020331

Interpretive Summary: Evolution of influenza A virus (IAV) in swine may result in unique viruses that pose a public health concern, and there have been a significant number of human infections from swine-origin IAV over the past decade. All circulating swine H3 subtype lineages are derived from human-to-swine interspecies transmission events and these lineages may retain human-transmissible capabilities. Contemporary H3 swine IAV exhibit significant genetic and antigenic diversity and current human seasonal vaccines or pre-pandemic candidate virus vaccines (CVV) may not protect adequately. In this report we used computational, serologic, and animal studies to perform a risk assessment of contemporary swine H3 IAV. We identified potential gaps in human vaccine coverage and demonstrated the utility of swine-to-ferret transmission experiments for risk assessment. Representative swine H3 viruses were efficiently transmitted from pig-to-ferret, indicating that these swine IAV represent a zoonotic risk.

Technical Abstract: Human-to-swine H3N2 influenza A virus (IAV) transmission occurs repeatedly and plays a critical role in swine IAV evolution and diversity. H3 1990.1 and 1990.4 lineages were introduced from human-to-swine in the 1990s, the 1990.4 diversified into 1990.4.A to 1990.4.F clades. Additional introductions occurred in the 2010s, establishing the 2010.1 and 2010.2 lineages. Human zoonotic cases, known as variants, have occurred from the 1990.4 and 2010.1 lineages highlighting a public health concern. If a human variant is antigenically drifted from current human seasonal vaccine (HuVac) strains, it may be chosen as candidate virus vaccine (CVV) for pandemic preparedness purposes. We assessed the zoonotic risk of US swine H3N2 strains by performing phylogenetic analyses of recent swine H3 strains to identify the major contemporary circulating genetic clades. Representatives were tested in hemagglutination inhibition (HI) assays with CVV or HuVac ferret antisera. The 1990.1, 1990.4.A and 1990.4.B.2 clade viruses displayed significant loss in cross-reactivity to CVV and HuVac antisera, and interspecies transmission potential was subsequently investigated in a pig-to-ferret transmission study. Strains from three lineages were transmitted from pigs to contact ferrets via respiratory droplets, however there were differential virus shedding profiles. These data suggest that existing CVVs may have limited protection and the contemporary 1990.4.A represent a specific concern given widespread circulation among swine in the United States and association with multiple zoonotic cases.