#16,236
The past 130 years of influenza pandemics (see above) depicts an interesting pattern; in modern times all flu pandemics have been caused by either H1, H2, or H3 viruses. While there's speculation that other subtypes (or possibly coronaviruses) may have caused pandemics in the distant past, we don't have much solid evidence for anything before 1900.
The H1N1 flu virus, which emerged in the 1918 pandemic, held sway until it was replaced by H2N2 in the 1957 `Asian Flu' pandemic. Eleven years later (1968) an H3N2 (aka `Hong Kong') flu virus emerged, supplanting H2N2.
Up until this point, we'd seen only one influenza A virus circulate at a time. All of that changed, somewhat mysteriously, in 1977 when H1N1 returned after an absence of 20 year. There has long been speculation that H1N1 escaped from a Chinese or Russian lab, but that remains unproven.
This time, the returning H1N1 virus - which sparked a pseudo-pandemic primarily affecting those under the age of 20 - did not replace H3N2. Instead, we had two co-circulating influenza A viruses to contend with, with one or the other dominating each successive flu season (alongside influenza B).
In the mid-2000s, with both H3N2 and H1N1 showing their age, thoughts turned to what flu subtype would likely emerge to replace them. Avian influenza (H5N1) was a concern, but H5 flu viruses had never (to our knowledge) sparked a human pandemic.
With an H1 and an H3 virus already in circulation, the return of H2N2 - which was last seen in humans in 1968 - seemed most likely. H2 viruses still existed in the wild (mostly in birds), and an H2 virus would be expected to differ enough antigenically from current flu viruses to pose a pandemic threat.
Nature, never one to abide by a script, threw us a curveball in the spring of 2009, and dealt up a new, swine-origin, H1N1 pandemic virus. It quickly supplanted the old H1N1 virus - in circulation since 1977 - but was unable to dislodge the H3N2 virus.
While we now know that it doesn't necessarily require a subtype change to spark a pandemic, H2N2 remains a plausible candidate to spark the next influenza pandemic.
Over the past dozen or so years we've looked at H2Nx in the wild, including:
- 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 2012, a PLoS One article (Recently Emerged Swine Influenza A Virus (H2N3) Causes Severe Pneumonia in Cynomolgus Macaques) found this swine H2N3 produced greater pathogenicity in a non-human primate than did the human H2N2 virus (see entry below).
- 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 CIDRAP On Mutated Swine Flu Virus).
With anyone under the age of 55 unlikely to carry any acquired immunity to H2N2 - should a novel H2Nx virus emerge now or in the future - it would find a target rich environment. A situation that was concerning enough that a decade ago several researchers suggesting adding an H2 component to the seasonal flu vaccine (see Nature: A Preemptive H2N2 Vaccine Strike?).
While that idea never gained traction, the need to be able to quickly develop and produce an H2Nx flu vaccine hasn't gone away.
This week, the HHS and BARDA invested nearly $35 million dollars in developing two H2Nx vaccine candidates (see Seqirus press release below) for just such a contingency.
Seqirus Awarded U.S. Government Contract to Develop Two Pandemic Influenza Vaccines
• Seqirus will develop and evaluate two influenza A(H2Nx) virus vaccine candidates in support of U.S. government pandemic preparedness objectives• Company will utilize its combination of cell-based and adjuvanted influenza vaccine technologies, as well as its next-generation self-amplifying mRNA platform• Multi-year contract with Biomedical Advanced Research and Development Authority (BARDA) builds on longstanding, successful public-private partnership to provide rapid vaccine manufacturing response in an influenza pandemic
Summit, NJ, USA 04 Oct 2021
Seqirus, a global leader in influenza prevention and a business of CSL Limited (ASX:CSL), today announced that the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), has selected Seqirus to develop two influenza A(H2Nx) virus vaccine candidates for assessment in a Phase 1 clinical study with the goal of helping to safeguard communities in the event of an influenza pandemic.1
Under terms of the multi-year, $34.95 million agreement, Seqirus will provide clinical development services to evaluate the safety, immunogenicity and dose-sparing capability of two influenza A(H2Nx) vaccine candidates:1
- The first candidate will utilize a combination of cell-based and adjuvanted technologies, building on Seqirus’ highly flexible combination platform technology used by AUDENZ™ (Influenza A(H5N1) Monovalent Vaccine, Adjuvanted), the first-ever adjuvanted, cell-based influenza vaccine, which was approved by the U.S. Food and Drug Administration in 2020 for use in a pandemic.2
- The second candidate will utilize Seqirus’ next-generation self-amplifying mRNA (sa-mRNA) platform, which has demonstrated promise as compared to more traditional influenza vaccine technologies in preclinical research.3
Preparing for the next pandemic never really stops. While H2Nx is a highly plausible cause of the next pandemic, it isn't alone. The CDC maintains a long (and growing) IRAT list of novel zoonotic viruses with at least some pandemic potential.
A couple of times each year influenza researchers meet to determine what novel viruses should be developed into Candidate Vaccine Viruses (CVVs). Over the past 2 decades more than 5 dozen H5, H9, H1, H3, and H7 CVVs have been selected by WHO for development.
Many of these older CVVs are for viruses that no longer circulate in the wild, having been supplanted by newer versions.
We should be getting a fall update from the WHO on Candidate Vaccine Viruses soon. While having the right CVV in the pipeline doesn't guarantee the rapid development and deployment of a pandemic vaccine, it should shorten the time to delivery by weeks or even months.
At least. That's the plan.
