The known history of influenza pandemics going back more than 125 years has been a repeating pattern of H1, H2, and H3 viruses (H2, H3, H1, H2, H3, H1 . . .) prompting the question: `Are Influenza Pandemic Viruses Members Of An Exclusive Club'.
Novel H1, H2, and H3 flu viruses appear to have fewer barriers to overcome in order to jump to humans - and while that doesn't preclude the breakthrough of an H5, H7, or H9 outlier - it suggests we should expect an H2 virus to eventually return as a pandemic threat.
This is hardly a new idea.
A press release on this research warned:
1950s pandemic influenza virus remains a health threat, particularly to those under 50
St. Jude Children's Research Hospital scientists report that avian H2N2 influenza A viruses related to 1957-1958 pandemic infect human cells and spread among ferrets; may aid identification of emerging threats.
And we revisited the topic in 2018, in J.I.D.: Population Serologic Immunity To H2N2 For Pandemic Risk Assessment, which warned: Population immunity to H2 viruses is insufficient to block epidemic spread of H2 virus. An H2N2 pandemic would have lower impact in those born before 1968.
While it doesn't get much press, avian H2N2 (and other H2 subtypes) continue to circulate in the wild. A few we've covered include:
- In 2019 we looked at Viruses: Molecular Characterization of a Novel Avian Influenza A (H2N9) Strain Isolated from Wild Duck in Korea in 2018
- In 2017, in H2N2: Everything Old Is Flu Again, we saw a study published in The Journal Of Veterinary Medical Science, which detailed the finding of H2N2 in Siberian Muskrats. (see Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia).
- In 2016's A Novel Reassortant H2N8 In China, described an H2N8 avian flu virus was isolated from a domestic duck in Zhejiang Province, Eastern China, in 2013.
- In 2006 and early 2007, a reassorted H2N3 subtype was detected in pigs on two different Missouri farms, which was the first known appearance of an H2 virus in a mammal since it was supplanted by the H3N2 virus in 1968 (see Recently Emerged Swine Influenza A Virus (H2N3) Causes Severe Pneumonia in Cynomolgus Macaques).
All of which brings us to an excellent review article, recently published in the journal Vaccine, which looks at the history of H2N2, and our waning population immunity to this influenza subtype.
Since this is a lengthy, and detailed, review I've simply reposted the link, abstract, and a brief excerpt. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Seven decades after the Asian influenza pandemic: A historical review about immunity and vaccines against H2N2
Alina Tscherne a, Florian Krammer
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https://doi.org/10.1016/j.vaccine.2026.128467Get rights and content
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Abstract
In 1957, a reassortant influenza A virus (IAV) H2N2 subtype emerged in humans and encountered a population that was antigenically naïve to this subtype. The lack of pre-existing immunity to the H2 hemagglutinin (HA) facilitated efficient human-to-human transmission, and by the end of the Summer of 1957, most countries around the world reported increasing influenza cases caused by the new influenza virus subtype. The pandemic lasted until 1958, resulting in millions of infections globally, with 1–4 million estimated deaths.
The first vaccines targeting specifically the H2N2 subtype were available in autumn 1957, but their limited immunogenicity hampered a successful fight against the “Asian influenza pandemic”. After the pandemic, H2N2 became seasonal in the following years. Most individuals developed immunity against both the H2 HA and N2 neuraminidase (NA) proteins of the virus, and vaccines administered in the early 1960s successfully boosted this immunity.
In 1968, the circulating H2N2 was replaced by the H3N2 subtype, and individuals with pre-existing N2 immunity were partially cross-protected against severe H3N2 infection, as the two N2 NAs were antigenically similar. Since the disappearance of H2N2 from the human population in 1968, global H2 immunity has been decreasing.
This raises concerns about a possible re-emergence of the H2 subtype from animal reservoirs, where the virus has circulated for decades, into the human population. As preparedness for future pandemics, research on H2-specific vaccines is currently ongoing, with several candidates being tested in preclinical studies and early-phase clinical trials. In contrast to 1957, vaccine technology platforms, but also the assays used to assess vaccine immunogenicity, and efficacy, have significantly improved.
This review aims to summarize the key historical milestones of the Asian influenza pandemic, the impact of H2N2 immunity during and after the 1957 pandemic, the immunogenicity of H2N2-specific vaccines in both a pandemic and pre-pandemic situation, and H2N2-specific antiviral treatment.
(SNIP)
(SNIP)It has been almost 70 years since the H2N2 pandemic and almost 60 years since the virus disappeared from the human population. The virus is still circulating in the avian reservoir, sometimes close to high-density urban areas like New York City, and the risk for another H2 pandemic has increased, as most of the population is now susceptible to H2.
Although vaccine technologies have improved, inducing strong immune responses to influenza viruses to which individuals are naïve remains challenging as seen with H5N1 and H7N9 vaccines. Furthermore, far less effort is being put into preparing for a potential H2 pandemic than into pandemic preparedness for H5N1. However, the H2N2 subtype has already demonstrated its ability to cause a pandemic, while H5N1 – despite very high prevalence in animals globally – has not yet resulted in a pandemic.
This process was repeated again in 1968 after an avian H3 virus - somewhere in Asia - reassorted with H2N2, producing the H3N2 virus. While I was only 3 for the H2N2 pandemic - and don't really remember it - I was in high school for H3N2.
While there are other routes by which an influenza pandemic can emerge, this is the classic scenario, and one that can be repeated at any time with no warning.
While it is always possible the next influenza pandemic will be an H1Nx, an H3Nx, or something more exotic (H5, H7, H9, etc.); waning population immunity makes an H2Nx virus increasingly likely.
While we can't know what pathogen will spark the next flu pandemic - or when it will arrive - we can take steps to be better prepared to deal with it.
Assuming, of course, that we can be bothered.