A paradox has existed at the centre of influenza research that has confounded scientists for decades: if influenza is as variable as commonly thought then why does just a single strain of influenza dominate each season?
Why not 10, 20, 50 or even 1,000 strains?
Logically a highly variable virus should produce a variety of different ‘offspring’. Mathematical models derived in Oxford 10 years ago controversially predicted that this paradox could be resolved by hypothesising the existence of regions of the virus that were easy to induce a protective immune response against but also limited in variability - essentially stating that influenza wasn’t as variable as commonly thought. The various forms of these regions would reappear and disappear as the immunity built up in the population by influenza infection changed over time (Recker et al. 2007).
Ten years on, these regions have been identified and shown in Thompson et al 2018 to dictate immunity to influenza in various age groups of humans. Laboratory assays used to detection antibodies showed that young children aged 6 to 12 had immunity to historical influenza strains that they could never have possibly experienced, one of which that last circulated in 1934! Mutagenesis of the regions of limited variability in various historical viruses removed this immunity. Furthermore, vaccination of mice with these regions of the influenza virus produced an identical pattern of immunity to that of the children.
For example, the mice vaccinated with either the region from the influenza virus circulating in 2006 or 1977 were protected against infection with an influenza virus that last circulated in 1934, replicating the immunity seen in children aged 6 to 12. Vaccination with just four variants of the region of limited variability was able to elicit immunity to all historical influenza strains. As these regions periodically reappear and disappear over time, vaccination with all of the possible variants will provide protection again future influenza too (Thompson et al. 2018).
These findings act as the basis for our vaccine.
We have identified a number of regions of limited variability which, if vaccinated against, enable protection against all influenza strains. The vaccine itself requires two doses to focus the immune response on the regions of limited variability, providing potentially life-long protection against flu.
As our vaccine concept is new but vaccine technology is not, we can use established techniques, such as E.coli based production, to reduce the cost and increase the efficiency of manufacturing the vaccine.
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