Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 influenza A viruses with loss in reactivity to human vaccine virus antisera as measures of relative zoonotic risk

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.

Pandemic Risk Assessment for a Swine Influenza A Virus in Comparative Human Substrates

“…The GA/19 virus was isolated from a Hampshire gilt, 4-H show pig that developed a fever and died suddenly after travel to an event (14,15), so we sought to assess GA/19 infection in healthy pigs. Clinical symptoms in infected pigs were mild, as seen in experimental infections with other swine influenza viruses following intranasal inoculation (31,32). Viral titers in BAL fluid averaged 2.00e5 pfu/mL at day 2 post-infection, decreasing slightly at day 4 post-infection to 1.56e5 pfu/mL (Figure 4).…”

Potential pandemic risk of circulating swine H1N2 influenza viruses

“…1C), and have exhibited sporadic human spillover events 51 . Previous representatives of the α-swH1N2 clade were shown to have antigenic distance from human vaccine strains, reduced recognition by human sera from two different cohorts 6 , and transmitted efficiently from infected pigs to naive recipient ferrets 52 . While highly efficient at controlling antigenically similar influenza viruses, antibodies directed towards HA become less effective over each subsequent flu season as surface glycoproteins rapidly mutate through antigenic drift.…”

Potential pandemic risk of circulating swine H1N2 influenza viruses

“…1C), and have exhibited sporadic human spillover events 51 . Previous representatives of the α-swH1N2 Article https://doi.org/10.1038/s41467-024-49117-z clade were shown to have antigenic distance from human vaccine strains, reduced recognition by human sera from two different cohorts 6 , and transmitted efficiently from infected pigs to naive recipient ferrets 52 . While highly efficient at controlling antigenically similar influenza viruses, antibodies directed towards HA become less effective over each subsequent flu season as surface glycoproteins rapidly mutate through antigenic drift.…”