#17,862
While `big-ticket' pandemic contenders like HPAI H5, H7N9, MERS-CoV, Nipah, and Disease X - all thought capable of killing tens of millions of people - get the bulk of our attention, there are scores of `lesser' pandemic threats in the wild that are probably more likely to emerge.
In 2009, we saw a swine H1N1 virus jump to humans, rapidly supplanting the existing seasonal H1N1 virus. While younger people were disproportionately affected, the pandemic turned out to be relatively mild.
Similar, mild-to-moderate influenza pandemics occurred in 1968 (H3N2) and 1957 (H2N2), while the 1918 H1N1 pandemic represents a far more severe event. But even relatively mild pandemics are costly, both in terms lives lost and/or disrupted and the global economy.
The CDC maintains a list (IRAT) of (currently) 24 novel flu viruses with zoonotic potential which ranks their threat by likelihood to emerge, and potential impact.
- Impact (i.e. severity) scores run from low 2.4 (A(H1N1) [A/duck/New York/1996]) to a high of 7.5 (A(H7N9) [A/Hong Kong/125/2017]).
- Emergence scores run from a low of 2.3 (A(H1N1) [A/duck/New York/1996]) to a high of 7.5 (A(H1N1) A/swine/Shandong/1207/2016]).
In the middle of the pack are three 3 North American swine variant viruses thought to have at least some pandemic potential (2 added in 2019). Emerge Impact
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
Since there are so many continually changing swine variant viruses in circulation these are basically representative viruses. Scores of similar - but genetically distinct - variants are in circulation around the globe, most of which are not monitored.
In late November the UKHSA Announced the 1st H1N2v (Swine Variant) Infection In the UK, in an individual who apparently tested positive in early November. The patient reportedly had mild illness and has recovered, but their source of infection was unknown.
In this case, the virus was a Eurasian clade H1 1B.1.1 H1N2v virus. We've seen other H1N2 variants of various lineages spill over into humans in the United States, Canada, Brazil, Taiwan, and several European countries.
While there is no way to know whether H1N2v will ever make the leap to becoming a pandemic virus - and if so, what lineage will prevail - there is value in understanding which strains are most likely to pose a threat.
To that end we have a preprint, published last week, that looks at the pandemic potential of two H1N2v lineages from North America. This is a lengthy report, so I've only posted the Abstract and excerpts from the discussion.
Follow the link to read it in its entirety. I'll have a postscript after the break.
Potential pandemic risk of circulating swine H1N2 influenza viruses
Valerie Le Sage, Nicole C. Rockey, Kevin R. McCarthy, Andrea J. French, Meredith J. Shephard, Ryan McBride, Jennifer E. Jones, Sydney G. Walter, Joshua D. Doyle, Lingqing Xu, Dominique J. Barbeau, Shengyang Wang, Sheila A. Frizzell, Lora H. Rigatti, Michael M. Myerburg, James C. Paulson, Anita K. McElroy, Tavis K. Anderson, Amy L. Vincent Baker, Seema S. Lakdawala
doi: https://doi.org/10.1101/2024.01.05.574401
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ABSTRACT
Influenza A viruses in swine have considerable genetic diversity and continue to pose a pandemic threat to humans. They were the source of the most recent influenza pandemic, and since 2010, novel swine viruses have spilled over into humans more than 400 times in the United States. Although these zoonotic infections generally result in mild illness with limited onward human transmission, the potential for sustained transmission of an emerging influenza virus between individuals due to lack of population level immunity is of great concern.Compiling the literature on pandemic threat assessment, we established a pipeline to characterize and triage influenza viruses for their pandemic risk and examined the pandemic potential of two widespread swine origin viruses.Our analysis revealed that a panel of human sera collected from healthy adults in 2020 has no cross-reactive neutralizing antibodies against an α-H1 clade strain but do against a γ-H1 clade strain.Swine H1N2 virus from the α-H1 clade (α-swH1N2) replicated efficiently in human airway cultures and exhibited phenotypic signatures similar to the human H1N1 pandemic strain from 2009 (H1N1pdm09).Furthermore, α-swH1N2 was capable of efficient airborne transmission to both naïve ferrets and ferrets with prior seasonal influenza immunity. Ferrets with H1N1pdm09 pre-existing immunity had reduced α-swH1N2 viral shedding from the upper respiratory tract and cleared the infection faster. Despite this, H1N1pdm09-immune ferrets that became infected via the air could still onward transmit α-swH1N2 with an efficiency of 50%. Taken together, these results indicate that this α-swH1N2 strain has a higher pandemic potential, but a moderate level of impact since there is reduced replication fitness in animals with prior immunity.
(SNIP)
Protection against emerging influenza virus strains in hosts without neutralizing antibodies can be conferred from CD8+ T cells, which recognize conserved internal influenza virus proteins. Although prior adaptive immunity may not prevent influenza virus infection, CD8+ T cells that display cross-reactivity against different subtypes of influenza virus have been linked to more efficient clearance of virus and faster recovery from illness58-60.Indeed, prior immunity to human seasonal viruses was not protective against a-swH1N2 airborne infection (Figure 3C and D). Encouragingly, experimentally infected ferrets with pre-existing immunity were able to clear a swH1N2 faster and H1N1pdm09 immunity resulted in an overall decrease in virus shedding over time (Figure 5B) and decreased lung pathology early during infection (Extended Data Fig. 5).However, the lack of disease severity in immune animals may also provide an opportunity for this virus to spread undetected and gain a foothold in the population, creating a pandemic risk. Taken together, our data demonstrate that this a-swH1N2 virus strain poses a high pandemic risk that warrants continued surveillance efforts to capture zoonotic events and an increased campaign to vaccinate swine against this H1 clade to reduce the amount of virus in source populations.
An avian H5 or H7 pandemic might be far more impactful, but history suggests that H1, H2, and H3 viruses have less of a `jump' to make to adapt to humans, and are therefore a more likely candidate to spark the next pandemic.
