Influenza A viruses (IAVs) found in swine pose a significant risk to human health due to their genetic diversity and lack of widespread immunity among populations. A recent study published in Nature Communications has focused on characterizing influenza viruses, particularly highlighting the α-H1N2 virus, to assess its potential to initiate a future pandemic.
Evolution of Swine Influenza
Influenza viruses have a unique ability to evolve, facilitating their transmission across species. While wild aquatic birds are the primary reservoir for these viruses, pigs also serve as critical hosts and mixing vessels for various influenza virus gene segments. This interplay underscores the ongoing threat of future pandemics and emphasizes the importance of monitoring and understanding circulating swine viruses.
Key genetic determinants such as Neuraminidase (NA) and Hemagglutinin (HA) undergo seasonal evolution through antigenic drift, influencing virus transmissibility, infectivity, host specificity, and pathogenicity.
Three main subtypes of endemic IAVs—swH1N1, swH1N2, and swH3N2—predominate among swine populations. The H1 classical swine lineage (1A) includes the α-H1 (1A.1), β-H1 (1A.2), and γ-H1 (1A.3) clades, while the swine lineage (1B) comprises the δ-H1 (1B.2) clades. In the United States, human infections have primarily involved variants such as 18 H1N1, 35 H1N2, and 439 H3N2.
Recent swine IAVs have demonstrated reassortment between swine, avian, and human origin viruses. Further antigenic drift in HA and NA may lead to the emergence of novel viruses against which human populations lack immunity.
Study Overview
The study has developed a decision tree framework to characterize and evaluate the pandemic potential of endemic swine IAVs. Utilizing extensive research since the 2009 H1N1 pandemic, both in vitro and in vivo methods were employed.
Specific focus was given to assessing the pandemic potential of the α-H1 (1A.1.1.3) clade strain A/swine/Texas/A02245420/2020 (α-swH1N2) and the γ-H1 (1A.3.3.3) clade strain A/swine/Minnesota/A02245409/2020 (γ-swH1N1). These clades were selected based on their geographical distribution, detection frequency, interspecies transmission from pigs to ferrets, documented human variant occurrences, and reduced cross-reactivity with human seasonal vaccines.
Study Findings
Previous investigations indicated that α-swH1N2 strains exhibited significant antigenic distance from human vaccine strains, resulting in reduced transmission efficacy from pigs to ferrets and diminished recognition by human sera. This lack of cross-neutralizing antibodies against α-swH1N2 in ferrets immunized with H1N1pdm09 or H3N2 underscores the limited immunity generated by initial seasonal virus exposure.
Variable levels of anti-N2 antibodies were observed across different birth cohorts, suggesting potential protection offered by NA-based immunity in specific sub-populations.
Research further demonstrated that pre-existing immunity from divergent strains could impact susceptibility to heterosubtypic viruses. In ferrets, α-swH1N2 transmission via airborne routes was efficient regardless of prior immunity status, although animals with existing immunity exhibited milder disease symptoms. This phenomenon may explain the lower severity observed during the 2009 pandemic.
In the absence of neutralizing antibodies, CD8+ T-cells play a crucial role in protecting against emerging influenza strains by recognizing conserved internal virus proteins. This immune response has been linked to accelerated recovery and enhanced viral clearance across influenza subtypes.
However, immunity to human seasonal viruses did not confer protection against airborne α-swH1N2 infection in ferrets. Despite this, previously immune ferrets demonstrated rapid virus elimination, reduced virus shedding duration, and less severe symptoms following α-swH1N2 exposure.
Conclusions
The study’s findings underscore the heightened pandemic risk posed by α-swH1N2 compared to γ-swH1N1 strains, necessitating enhanced surveillance to promptly detect zoonotic events. Additionally, targeted vaccination efforts aimed at swine populations within the H1 clade could mitigate viral circulation and reduce the likelihood of future outbreaks.
