Updating COVID-19 vaccines ‘on the agenda’, but not sustainable

When scientists first set out to find an effective vaccine for SARS-CoV-2, it was not expected that they would come up with so many options, let alone with such high efficacy rates.
 
The use of messenger RNA (mRNA) technology has been labelled by researchers as particularly exciting, primarily due to the faster rate at which it can be adapted for emerging variants.
 
And that has certainly been the case to date, with both Moderna and Pfizer leading the way in terms of producing updated vaccines to protect against the continually evolving virus.
 
In the second half of 2022, the Therapeutic Goods Administration (TGA) provisionally approved two updated bivalent vaccines – one by Moderna and the other Pfizer – currently in use in Australia as a booster for adults. Containing two mRNA components of the coronavirus, both vaccines target the original strain and Omicron variant BA.1.
 
Since then, Pfizer has developed an updated vaccine with a focus on Omicron strains BA.4 and BA.5, which was provisionally approved by the TGA on 20 January for use as a booster in people aged 12 and older. Moderna has developed a similar vaccine that was granted a provisional determination on 28 September 2022, but is still awaiting approval for use.
 
Associate Professor Paul Griffin, an infectious diseases physician at the University of Queensland, told newsGP there is ‘more happening than ever’ in the vaccine development space, and that mRNA is continually proving to be ‘exceptional technology’ for COVID-19.
 
But while updating the vaccines to target specific strains of the virus as it evolves is still ‘high on the agenda’, it is not a strategy he foresees being successful long-term.
 
‘Even though it’s relatively quick to be able to update the vaccines, there still is a process associated with that,’ Associate Professor Griffin said.
 
‘If we were to rely solely on that strategy, we’d essentially be chasing our tail to a degree and probably asking for people to have more vaccines than many will accept.
 
‘I think we’re seeing that a little with the first iteration of their improved bivalent vaccine.’
 
Vaccine uptake has certainly been lagging since the widespread removal of vaccine mandates. Since booster shots were made available in November 2021 and the first bivalent vaccine by Moderna in October 2022, 72.4% of the eligible population had received a third dose by January 2023, and 44.6% had received a fourth.
 
So where to next?
 
One strategy anticipated by Associate Professor Griffin is combining more viral targets into the one vaccine, similar to the approach taken for influenza.
 
‘So going from bivalent to maybe combining a few different subvariants, particularly as we see the greater development of new subvariants potentially accelerate,’ he said.
 
‘Many have described that as a “variant soup”, where there’s just so many we’re watching, a bit like we did with the flu vaccine. We went from having three to having four, and four is probably the best strategy.
 
‘We might end up doing something similar with COVID vaccines.’
 
Following that, the infectious diseases expert says one of the things scientists are now trying hardest to address is people’s ability to still get infected after they have been vaccinated – so-called ‘transmission blocking’ vaccines.
 
‘The intra-nasal vaccines look really promising there,’ Associate Professor Griffin said.
 
‘Another strategy is what some are describing as a “pan-coronavirus” vaccine.
 
‘That’s potentially a little too ambitious, but at least one that covers far more circulating subvariants than we are at the moment, that might just be a bit longer lasting and less in need of an update quite as regularly.’
 
With people aged 18 and over set to become eligible for a fifth dose from 20 February, the Department of Health and Aged Care (DoH) told newsGP that Australia currently has four million doses of Pfizer’s bivalent BA.1 COVID-19 vaccine available for administration, with 10 million doses of Pfizer’s bivalent BA.4/5 vaccine scheduled for delivery in February 2023.
 
‘They will become available for administration at sites from 6 March,’ a DoH spokesperson confirmed.
 
‘The Government has secured sufficient doses to complete current and future booster requirements and any new or remaining primary course vaccinations.
 
‘This diverse portfolio of vaccines provides Australians flexibility of choice and enables the Government to address variants of concern in the future.’
 
In preparation of its rollout, the Australian Technical Advisory Group on Immunisation (ATAGI) issued guidance for the use of Pfizer’s latest bivalent vaccine in people aged 12 and over earlier this month.
 
It notes research that shows those who received the Pfizer bivalent BA.4/5 vaccine developed higher neutralising antibody titres than those who received Pfizer’s original vaccine, with higher neutralisation of newer BQ.1.1 and XBB.1 subvariants also.
 
One US study showed vaccine effectiveness against hospitalisation or death with a bivalent BA.4/5 booster (either Pfizer or Moderna) was 61.8% compared with an original booster (24.9%).
 
However, it is noted that receiving a booster – whether bivalent or an original vaccine – is the priority, and provides ‘significant protection’ from severe disease against Omicron subvariant infections.
 
While Associate Professor Griffin agrees, and says the current vaccines are still fundamentally the ‘right vaccines to use’ with the benefits continuing to outweigh the risks, he says waning protection due to immune evasion does raise some questions around the longevity of protection.
 
‘It is perhaps less than we’d like to see at the moment,’ he said.
 
‘So that’s why we do need to have improvements in the vaccines to continue to get the protection that we need. But the most important thing is even with all these issues we discuss, there still has yet to be a subvariant or a variant to which our vaccines don’t work.
 
‘So, it’s certainly not the case they’ve been rendered ineffective, and having a recent booster still is excellent protection, particularly in severe disease, but even against some of those early endpoints like ability to be infected.’
 
In the meantime, scientists are also sharply focused on developing combination vaccines targeting COVID-19 and other respiratory viruses, such as the influenza and respiratory syncytial virus, in the hopes that it will reduce the number of vaccinations required and improve uptake.
 
‘A lot of those are using mRNA technology,’ Associate Professor Griffin said.
 
‘With RSV, we’ve obviously never had an approved vaccine before, but being able to protect against all three in a single vaccine, or even just COVID and the flu, will be a big step forward for acceptability and uptake.’
 
When it comes to combination vaccines, Pfizer and Moderna appear to be leading the way, as does Novavax, with a clinical trial for a COVID-19 and flu vaccine underway in Australia and New Zealand.
 
While the initial impression given by commentators on mRNA may have been a simpler path to update vaccines, it is the virus itself, not the technology, that Associate Professor Griffin says has impacted the timeline of both vaccine development and getting shots into arms.
 
‘This virus has thrown just so many challenges at us because it’s a truly novel pathogen; it’s been impossible to predict what it was going to do and the rate of emergence of increasing immune evasion and subvariants has been a huge challenge for us,’ he said.
 
‘It doesn’t take away at all from just how big an achievement it was to have vaccines as successful as we did at the start of the pandemic. But this virus is just continuing to evolve and so we do need to look to strategies to address that, and there’s lots of really good work happening on that front.
 
‘So, I think we’ll see some iterative steps in the right direction probably this year.’
 
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