Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 Influenza A viruses with reduced reactivity to candidate vaccine virus antisera as measures of relative zoonotic risk

Authors: KIMBLE, J. BRIAN - Oak Ridge Institute For Science And Education (ORISE); SOUZA, CARINE - Oak Ridge Institute For Science And Education (ORISE); 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); LEWIS, NICOLA - Royal Veterinary College; DAVIS, C. TODD - Centers For Disease Control And Prevention (CDC) - United States; THOR, SHARMI - Centers For Disease Control And Prevention (CDC) - United States; Baker, Amy

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/26/2022
Publication Date: 10/29/2022
Citation: Kimble, J., Souza, C.K., Anderson, T.K., Arendsee, Z.W., Hufnagel, D.E., Young, K.M., Lewis, N.S., Davis, C., Thor, S., Baker, A.L. 2022. Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 Influenza A viruses with reduced reactivity to candidate vaccine virus antisera as measures of relative zoonotic risk. Viruses. 14(11). Article 2398. https://doi.org/10.3390/v14112398.
DOI: https://doi.org/10.3390/v14112398

Interpretive Summary: Influenza A viruses (IAV) are endemic in both humans and pigs and these viruses readily move between hosts. This interspecies transmission increases viral diversity and has great impact on viral ecology in both hosts. Swine origin IAVs have the potential to initiate human pandemics and are of great importance to pandemic preparation efforts. Because of this, swine origin IAVs have been used to generate pandemic preparedness candidate vaccine viruses (CVV) , but the efficacy of these vaccines against contemporary viruses is unclear due to viral evolution. In this report we used computational, serological and in vivo studies to perform a risk assessment of contemporary swine H1 IAVs. We identified potential gaps in vaccine coverage and demonstrated the utility of swine-to-ferret transmission experiments to enhance risk assessment.

Technical Abstract: During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population.