While there are legitimate concerns over the potential for HPAI H5, or H7 viruses to spark a human pandemic, as we've discussed often over the years (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?), the progression of human influenza pandemics over the past 130 years has been H2, H3, H1, H2, H3, H1, H1 . . .
Novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while they might not prove as virulent as H5 & H7 avian subtypes - that puts them at or near the top of our pandemic threats list.
Every year since 2010 we've seen anywhere from a handful to several hundred swine-origin influenza cases detected in humans, primarily connected with state and local agricultural fairs. Less well documented, we've also gotten reports of swine-origin influenza jumping to humans in Europe and Asia.
Spillovers of swine variant viruses to humans are thought to be significantly under-reported, with some estimates suggesting fewer than 1% of cases are ever ever confirmed (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought.
The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).
H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 ModerateH3N2 variant [A/Ohio/13/2017] Jul 2019 6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011] Dec 2012 6.0 4.5 Moderate
In addition to the 3 North American swine-variant viruses on the CDC's IRAT list, we continue to watch the evolution of China's EA H1N1 `G4' virus, Brazil's H1N2v virus, and emerging variants (and spillovers) in Europe (see ANSES Reports A `New' Swine Flu Virus Has Taken Over Other Genotypes in France).
But the reality is, most of the world isn't bothering to test for - or to share reports on - swine influenza.
Researchers tested blood samples from 4 cohorts; pig workers, veterinarians, Philadelphia flu-vaccine recipients, and Hong Kong residents for antibodies against seasonal flu and an array of H1/H3 swine-influenza viruses in circulating in U.S. swine.
While all four groups showed notable gaps in protective antibodies (HI titer ≥40) against specific swine influenza A virus (IAV) strains, swine-exposed workers had the lowest overall seropositivity to several high-risk strains.
The authors wrote:
Individuals occupationally exposed to swine, such as Veterinarians and Farm Employees, were significantly less likely to have protective antibody levels against contemporary IAV in swine. This group exhibited lower vaccination rates and reduced seropositivity, particularly swine farm employees, underscoring a heightened risk of zoonotic infection.
The authors also report (out of 10 representative swine IAVs tested) - that based on population immunity - 4 strains had even lower R0 (r-naught) thresholds than the 2009 H1N1 pandemic.
Swine strains representing HA clades 1A.1.1.3, 1A.3.3.3-c-1, 1B.2.1, and 1B.2.2.2 demonstrated elements of increased pandemic risk, including low population immunity, lack of cross-reactivity to human seasonal vaccine strains, and low thresholds of required human transmissibility.
Occupationally exposed and general population antibody profiles to influenza A viruses circulating in swine as an indication of zoonotic risk
Celeste A. Snyder, Garrett M. Janzen, Giovana Ciacci Zanella, Daniel C. A. Moraes, Gustavo S. Silva, Jefferson J. S. Santos, Elizabeth M. Drapeau, Scott E. Hensley, Tavis K. Anderson, Phillip C. Gauger, Amy L. Baker
doi: https://doi.org/10.64898/2026.01.08.26343691
This article is a preprint and has not been peer-reviewed
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Abstract
Individuals with occupational exposure to swine may have disproportionate risk for zoonosis with swine influenza A virus (IAV). To evaluate human antibody responses, sera or plasma from swine veterinarians, swine farm employees, and the general population were tested by hemagglutination inhibition (HI) assays against representative swine and human seasonal influenza vaccine strains. HI data were analyzed by antigenic cartography to assess strain relationships, and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles.
Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs 70%) and significantly lower odds of seropositivity to several H1 and H3 from swine compared to general population cohorts.
One swine strain exhibited significant antigenic drift (3.62 AU) from its nearest vaccine strain. Multiple strains required lower R₀ thresholds for pandemic spread (1.09-1.35) than recorded pandemic strains (1.46-1.80). This demonstrates that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.
Despite campaigns to get agricultural workers to increase their uptake of the seasonal flu vaccine, there is obviously a lot of work to be done in that regard. As we've discussed previously (see Nature: Reverse Zoonosis of the 2022–2023 Human Seasonal H3N2 Detected in Swine), flu transmission is a two-way street.
There remain huge gaps in surveillance of pigs, both here in the United States and around the world, which leaves us vulnerable to being blindsided (like we were in 2009) by an emerging swine flu virus.
And while that might not be as severe as H5N1, there are no guarantees that the next swine-flu pandemic will be as mild, or as short-lived, as the last one.
