Influenza A viruses (IAVs) in swine are a source of risk to human beings due to their high genetic diversity and absence of population-level immunity. A recent Nature Communications study characterizes influenza viruses, with a particular focus on the α-H1N2 virus, to determine their potential to cause a future pandemic.
Study: Potential pandemic risk of circulating swine H1N2 influenza viruses. Image Credit: Fahroni / Shutterstock.com
The evolution of swine flu
Influenza viruses possess the ability to evolve specific traits, which facilitates persistent transmission to new species. Although wild aquatic birds are the primary natural reservoir for these virus, pigs can also act as critical hosts and mixing vessel for viral gene segments of IAVs. This poses a threat to future pandemics, thus emphasizing the importance of monitoring and characterizing circulating swine viruses.
Neuraminidase (NA) and hemagglutinin (HA), which evolve seasonally due to antigenic drift, are key determinants of virus transmissibility, infectivity, host specificity, and pathogenicity.
Three endemic IAV subtypes, including swH1N1, swH1N2, and swH3N2, predominate in swine. The H1 classical swine lineage (1A) comprises the α-H1 (1A.1), β-H1 (1A.2), and γ-H1 (1A.3) clades, whereas the swine lineage (1B) includes the δ-H1 (1B.2) clades. In the United States, human infections have been primarily due to 18 H1N1, 35 H1N2, and 439 H3N2.
A reassortment between swine-, avian-, and human-origin viruses has been observed in recent swine IAVs. The antigenic drift of HA and NA may also lead to the emergence of novel viruses that the human population lacks immunity against.
About the study
The current study created a decision tree to aid in characterizing and assessing the pandemic risk of endemic swine IAVs. The decision tree utilizes the extensive research conducted since the 2009 H1N1 pandemic using both in vitro and in vivo methods.
The current study determines the pandemic potential of an 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 because of their geographical distribution, detection frequency, interspecies transmission from pigs to ferrets, reported human variant events, and loss in cross-reactivity against human seasonal vaccines.
Study findings
Previous studies have shown that representatives of the α-swH1N2 clade had antigenic distance from human vaccine strains, which led to differential transmission from pigs to ferrets and lower recognition by the human sera. Consequently, cross-neutralizing antibodies against α-swH1N2 in H1N1pdm09- or H3N2-imm ferrets were not detected in human sera, thus indicating that initial seasonal virus infection did not generate immunity.
Variable levels of anti-N2 antibodies were identified in human sera across all birth years. This finding implies that some level of protection could be provided by this NA-based immunity, at least in some sub-populations.
Prior research by researchers of the current study demonstrated that previously acquired immunity could affect the susceptibility to heterosubtypic viruses and that neutralizing antibodies do not mediate this type of immunity. Therefore, previously acquired immunity through divergent strains could influence the susceptibility of ambient viruses.
In fact, α-swH1N2 was efficiently transmitted through the air to ferrets, irrespective of their immune status. However, the severity of the disease was lower in animals with prior immunity. A similar phenomenon could explain the lower-than-expected mortality and morbidity during the 2009 pandemic.
In the absence of neutralizing antibodies, CD8+ T-cells can confer protection against emerging influenza virus strains, as these cells recognize internally conserved influenza virus proteins. In fact, CD8+ T-cells with cross-reactivity against subtypes of the influenza virus have provided rapid recovery from illness and more efficient clearance of the virus.
No protective effect of immunity to human seasonal viruses was noted with regard to α-swH1N2 airborne infection. Nevertheless, infected ferrets with prior immunity were found to successfully and rapidly eliminate α-swH1N2 while also exhibiting reduced overall virus shedding time and less severe symptoms as a result of H1N1pdm09 immunity.
Nevertheless, ferrets were still able to transmit H1N1pdm0 with an efficiency of 50%. Thus, H1N1pdm0 can spread undetected due to the lack of disease severity in immune animals and, as a result, create pandemic risk.
Conclusions
The study findings demonstrate that the α-swH1N2 virus strain poses a higher pandemic risk than the γ-swH1N1 strain, thus necessitating the need for additional surveillance efforts to detect zoonotic events in a timely manner. Additionally, more vaccination campaigns should be launched to protect swine from this H1 clade, which should aid in reducing viral circulation in source populations.