GP20: New weapon in fight against ‘ignored’ virus

The drastic measures applied to everyday life in Australia aimed at containing COVID-19 – from physical distancing and improved hygiene, to limited international travel – have seen national lab-confirmed influenza numbers drop to unprecedented levels.
 
In the nearly 11 months up until 18 November, only 21,233 cases have been reported nationwide, which is less than one third of the 70,000 registered in July 2019 alone. Flutracker has also recorded vastly lower rates of flu-like illness, despite an above average peak in January and February before coronavirus restrictions were first imposed.
 
The low level of transmission means Australia is at risk of a ‘rebound’ once borders open and new strains of the virus begin to circulate in the community, but a newly-available cell-based influenza vaccine has the potential to be a ‘substantial improvement’ on previous candidates, according to Griffith University’s Professor Paul Van Buynder.
 
Professor Van Buynder, Chair of the Australian Immunisation Coalition, made the remark during an on-demand session featured in GP20, in which he discusses the advantages of cell-based vaccines over those manufactured via traditional egg-based processes.
 
‘Influenza has largely been ignored this year because of the arrival of the pandemic and because we’ve seen a massive decrease in the amount of influenza in Australia,’ he said.
 
‘But while this year has been an aberration, last year 310,000 Australians had lab-confirmed influenza, and probably at least double that had influenza.
 
‘We estimated around 3000 deaths, mainly in the elderly and in settings such as long-term care, but 30 children died as well just due to influenza and its complications.’
 
Professor Van Buynder cited research conducted by the US Centers for Disease Control and Prevention (CDC) that showed vaccine effectiveness has varied from around 60% to just 19% efficacy over the past 15 years – with a 5% difference equivalent to around 80,000 influenza-hospitalisations.
 
‘This sort of picture is [also] what we [can] see in Australia, depending on what’s happening with the circulating strain, which influenza turns up and what’s happening with the influenza match between the vaccine and the circulating strain that arrives,’ he said.
 
‘Clearly, rather than concentrating on trying to vaccinate a few extra people, we really need to concentrate on trying to get a more effective vaccine to protect the people that we’re vaccinating.’
 
Patient, viral and vaccine factors can all drive this variability, according to Professor Van Buynder, and while the former two are more difficult to manage, changing the way vaccines candidates are developed has been shown to have a real-world impact.
 
‘We know that human flu viruses don’t always grow well in eggs … the viruses can actually adapt to make themselves grow better in the egg environment, but this can then cause mutations,’ he said.
 
‘Those mutations can produce viruses that are different to the selected reference strain, and then even though we have a close match between what circulates and what’s in the reference strain, our vaccine no longer is similar and we get a mismatch through that process.
 
‘So while we get high yield growth, we actually build a less robust immune response because of that.’
 
In comparison, cell-based influenza vaccines – which are manufactured in canine kidney cells – prevent the potential for egg adaptation, meaning there is less chance of generating a mismatch, even with notoriously volatile strains such as influenza A H3N2.
 
They can also be developed faster than egg-based vaccines, which are typically manufactured five or six months ahead of flu season based on an estimation of which strains will likely be circulating in the community.
 
‘People from influenza labs across the world get together with virologists and immunologists and [the World Health Organization] WHO and they make a recommendation each year in September for what strains should go in our vaccine that we start giving out in April,’ he said.
 
‘There’s a lot of time between when we make the decision based on the recommendations from the WHO and the Australian [Influenza] Vaccine Committee … six months later the actual virus that turns up may be quite different.
 
‘[But with cell-based vaccines] there’s a more rapid process of production and so we can actually
produce these more quickly and meet unexpected changes in demand.
 
‘The outcome is that the cell-based manufacturing avoids egg adaptation, and leads to a closer match to the WHO-selected strains at the end of the process.’
 
While the vaccine will be new to Australia, it has been employed extensively elsewhere, and recent US studies have shown them to be well-tolerated and potentially capable of delivering superior outcomes to egg-based vaccines.
 
‘This vaccine has now been around for one-and-a-half decades in Europe, and the quadrivalent formulation that we’re going to get was licensed four years ago and has had over 100 million doses distributed worldwide,’ Professor Van Buynder said.
 
‘It will be available next year, only via private prescription, and it’s only indicated for use in adults [and children] nine years of age and older.
 
‘Real world observational studies … suggest that there is a clinical benefit, but that is going to vary depending on the circulating strain, the degree of match of the circulating strain, and so on.
 
‘[In any case] there’s a real prospect that cell-based vaccines will be in some years, a substantial improvement on the egg-based vaccines.’
 
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cell-based vaccines flu influenza vaccination