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Preprint: Interspecies Transmission From Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A viruses

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  • Preprint: Interspecies Transmission From Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A viruses

    Preprint: Interspecies Transmission From Pigs to Ferrets of Antigenically Distinct Swine H1 Influenza A viruses

    Credit CDC FluView


    While relatively rare, over the past 6 weeks we've seen 7 novel swine-variant flu infections reported in people across the nation (3 H3N2 in West Virginia, 4 H1N2 in Michigan, Ohio, Oregon, Wisconsin). Given the low rate of influenza testing and sub-typing, there are presumably many more we are not aware of.

    Past studies (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012) have suggested that perhaps as few as 1 out of every 200 community cases are identified.

    A little over 2-weeks ago the CDC released a new HAN Advisory urging clinicians to ask flu patients about recent swine contact, and to forward samples from suspected cases to state or local health departments for analysis.

    While a novel flu pandemic could arise from a lot of sources (avian, swine, canine, equine, etc.), pigs are considered particularly high risk because they are susceptible to a wide range of flu viruses, they make excellent `mixing vessels' for influenza viruses, and they have been responsible for pandemics in the past.

    Although most swine variant viruses don't spread efficiently in humans, and most cases are mild or moderate, the CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least somepandemic potential (2 added in 2019).

    H1N2 variant [A/California/62/2018] Jul 2019 5.8 5.7 Moderate
    H3N2 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

    The CDC's Assessment of the Risk from these viruses reads:
    Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it’s possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website

    The United States doesn't have a monopoly on swine-variant viruses, and in recent years we've seen reports from Canada, Brazil, Germany, Denmark, France, Taiwan, and the Netherlands.

    Perhaps the most dangerous variant is currently circulating in China (see EID Journal: Zoonotic Threat of G4 Genotype Eurasian Avian-Like Swine Influenza A(H1N1) Viruses, China, 2020).

    While it is possible that the next influenza pandemic will emerge from an H5, H7, or H9 avian virus - or from some other non-porcine species - if you want to go with the odds, a swine variant is a pretty good bet.

    All of which brings us to a new preprint, published this past week by researchers at the USDA and the UK's Royal Veterinary College (Hertfordshire), which examines the transmissibility (in ferrets) of swine-variant viruses in the United States, and their reactivity to current flu vaccines.

    This 29-page report is detailed, and at times highly technical, but well worth reading. I've reproduced the abstract, and some excerpts below. I'll have a brief postscript after the break.

    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

    J. Brian Kimble, Carine K. Souza, Tavis K. Anderson, Zebulun W. Arendsee, David E. Hufnagel, Katharine M. Young, Nicola S. Lewis, C. Todd Davis, Amy L. Vincent Baker

    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.


    Influenza A virus (IAV) is endemic in both humans and pigs and there is occasional bidirectional transmission of viruses. The process of interspecies transmission introduces novel viruses that increases the viral diversity in each host, impacting viral ecology and challenging control efforts through vaccine programs. Swine-origin IAVs have the potential to cause human pandemics, and pandemic preparation efforts include the identification and generation of candidate vaccine viruses (CVV) derived from epidemiologically relevant swine IAV surface proteins.

    The CVVs are derived from swine IAV detected and isolated in humans, and are updated infrequently; consequently the efficacy of these vaccines against contemporary swine IAV is unclear given rapid turnover and change of diversity. In this report we perform a risk assessment of contemporary swine H1 IAVs, determine whether current CVVs cross-react, and illustrate how swine-origin IAV replicate, transmit, and cause disease in a swine-to-ferret model system. In doing so, we identify the swine IAV that have lost cross-reactivity to current pandemic preparedness vaccines and demonstrate the utility of swine-to-ferret transmission experiments to further inform risk assessment.


    Results of this study indicate that swine IAV from the US may escape vaccine immunity from CVV or seasonal vaccines as they continue to circulate and evolve in the swine population. Three H1 clades demonstrated antigenic drift away from available CVV antisera. Additionally, contemporary clade representatives showed the ability to transmit from pigs to ferrets, a gold standard for human influenza transmissibility. These data highlight the increased risk to human populations posed by H1 clades of swine IAV, particularly the 1A.1.1.3.

    Since the conclusion of these experiments in July 2020, there have been 15 H1 variant cases in North America where the HA clade could be determined; an additional 3 variants had insufficient data to identify the HA clade. Of these variant IAVs, 2 came from the 1A.1.1.3 clade, 4 were derived from the 1A.3.3.3 clade, 5 were from the 1A.3.3.2 clade, and 4 were from the 1B.2.1 clade.

    These data highlight the utility of swine-to-ferret transmission studies as a pandemic risk assessment tool and identifies the gaps in CVV coverage of US H1 swine IAV. The results stress the need to continually assess the intra-clade cross-reactivity of existing CVVs to identify and develop more contemporarily relevant pandemic preparedness strains.

    (Continue . . . )

    H1, H2, and H3 swine flu viruses are not considered reportable animal diseases to the OIE (now WOAH) - and like many others (avian H9N2, H6N1, H3N1, H10N8, etc.) - while they pose some risk of human infection, are poorly tracked.

    It's only when surveillance (which ranges from limited to non-existent) around the world picks up one or more human infections, or a research study is published, that we take notice.

    Our track record of predicting which virus will spark the next pandemic is abysmal, which is why we must follow so many threats. And still - as with COVID-19 and the 2009 H1N1 pandemic - we often get hit by something from out of left field.

    Swine variant viruses like the ones described in this paper could simmer quietly for years without ever sparking a pandemic. After all - with millions of pigs swapping viruses - if it were easy to generate a biologically `fit' pandemic strain, we'd be up to our hips in them all the time.

    But, rare as they are, pandemics do occur. And with so many potential sources for the next pandemic - and an increasingly mobile population to aid and abet its spread - the next pandemic is probably a lot closer than most people expect.

    Just over a year ago, in PNAS Research: Intensity and Frequency of Extreme Novel Epidemics, researchers suggested that the probability of novel disease outbreaks will likely grow three-fold in the next few decades.

    Which is why we should be preparing seriously now, lest we risk being caught flat footed and unprepared. Again.
    All medical discussions are for educational purposes. I am not a doctor, just a retired paramedic. Nothing I post should be construed as specific medical advice. If you have a medical problem, see your physician.