How a ‘lower-efficacy’ vaccine could take us to herd immunity

Ever since vaccine developers began releasing results from major phase 3 clinical trials, debate has raged in medical circles around which vaccine Australia should prioritise.
 
Achieving herd immunity via vaccination has been hailed as the final step on the path towards post-COVID normalcy, with the alternative being a continuation of social distancing, mask use and all of the other public health measures that have changed life so dramatically over the past 13 months.
 
As a result, the impressive efficacy of mRNA candidates produced by Pfizer/BioNTech and Moderna – upwards of 90% for each candidate – has seen some calls for the Australian Government to scrap its existing agreement with AstraZeneca, or at the very least pursue new deals to secure even more doses of the seemingly more efficacious vaccines.
 
Australia currently has deals in place for 20 million doses of the Pfizer/BioNTech vaccine, 54 million of Oxford University/AstraZeneca’s candidate, and 51 million of Novavax.
 
The argument is that the relatively low efficacy of the candidate developed by Oxford University/AstraZeneca – estimated to be around 62% – will not allow Australia to reach herd immunity, even if the country reached the all-but-impossible mark of 100% vaccine coverage.
 
But leaving aside the ancillary benefits that the Oxford University/AstraZeneca candidate possesses – such as less onerous cold-chain requirements and the fact it can be produced domestically – there is also an argument (albeit with the usual caveats regarding what remains unknown about COVID-19) that it could still take Australia to the immunity promised land.
 
While the Oxford University/Astrazeneca candidate may only stop fewer than two in three people from contracting the disease, it has so far displayed an ability to completely protect against severe disease and death. This appears to remain even when up against newer variants, which have dented the overall efficacy rates of most vaccine candidates.
 
This leads to the question: could Australia achieve herd immunity by combining the estimated 62% of people who are fully protected against the virus with the other 38% who may contract a form of the disease, but are highly unlikely to experience more than cold-like symptoms?
 
According to Professor Dale Godfrey, Immunology Theme Leader at the Doherty Institute, it is a possibility.
 
‘That does fit with what we currently know. But the caveat there is what we currently know can change,’ he told newsGP.
 
‘If you do get infected after having the vaccine, the infection may further boost your immunity. But whether it increases your immunity to the same level as another vaccine is unknown.
 
‘In theory, it should further boost your immunity and may mean you’re protected against further infection … [but] we have to keep in mind that we really are still learning and what seems pretty clear today might not be so clear tomorrow.’
 
Such a theory – like most associated with COVID-19 – contains a number of clauses.
 
‘One caveat here is that in the phase 3 [AstraZeneca] study, the number of individuals in the placebo group with severe disease was low – it was about 10,’ Professor Godfrey said.
 
‘It is also possible that a [post-vaccination] infection isn’t going to help very much, because there’s a lot about this virus that can suppress immunity.’
 
Despite the uncertainty, Professor Anthony Kelleher, Director of the Kirby Institute at the University of New South Wales, told newsGP it is definitely possible that natural infection would augment a vaccine immune response.
 
‘Someone who’s been vaccinated will have a boosted immune response by the infection and that will likely sustain the longevity of the immune response for longer,’ he said.
 
‘If you can convert this into a situation where the overwhelming majority of people who get infected end up with an upper respiratory tract infection, like the common cold, or at worst sort of a good case of the flu, then that’s a pretty good outcome.
 
‘Although it would be ideal to have something that was even better than the AstraZeneca candidate, we’re not in an ideal situation.
 
‘Preventing the overwhelming majority of severe disease is an excellent outcome.’
 
It is also important to note that vaccine efficacy is not the only variable that determines whether a population can achieve herd immunity.
 
Infectious diseases physician and microbiologist Associate Professor Paul Griffin, who ran the Australian arm of Novavax’s phase 1/2 trial last year, told newsGP that efficacy rates alone are not a good predictor of whether herd immunity can be achieved.
 
‘[Vaccine efficacy] is really useful for epidemiological modelling in a controlled system, but what we have in the real world is not a controlled system,’ he said. ‘The efficacy of a vaccine to achieve [herd immunity] can actually be altered by adding in additional interventions.
 
‘These efficacy figures that we’re hearing about have been conflated so much. We have to remember, they’re based solely on the primary endpoints of these trials, which is symptomatic cases that are microbiologically proven.
 
‘The whole concept of one of our vaccines not being able to achieve herd immunity because its efficacy rate is lower, when you think about it, is just so fundamentally flawed.’


Australia currently has a deal in place for 54 million doses of Oxford University/AstraZeneca’s vaccine candidate. (Image: AAP)

Professor Griffin pointed out that there is limited evidence as to how effective any of the vaccines are at stopping transmission.
 
‘We still don’t know with any of these vaccines, whether they blocked transmission by 0%, or 100%, or anywhere in between,’ he said.
 
‘To argue that Pfizer is better than AstraZeneca at doing that is just not supported by the data we have at hand.’
 
This is an important factor, as stopping transmission – in any form, including asymptomatic – is crucial for achieving herd immunity.
 
Dr Annette Marsh Fox, who specialises in infectious diseases, microbiology and immunology at the University of Melbourne, told newsGP herd immunity will only occur once we have a vaccine or form of immunity that guarantees people cannot continue to spread the virus, regardless of symptoms.
 
‘[Herd immunity] would depend upon the proportion of the 38% who fail to generate a fully protective immune response that actually get infected, and in turn on the non-pharmaceutical interventions that people use to avoid infection,’ she said.
 
‘Neutralising antibodies need to be maintained at protective levels to prevent infection, and once they get below that threshold – which is not actually known – infection could occur.’
 
And while infections that occur when immunisation does not provide full protection are ‘highly likely’ to induce additional protection, according to Dr Marsh Fox, there is no evidence they can prevent asymptomatic illness.
 
‘I’d be a bit doubtful that those who don’t develop symptomatic COVID-19 following vaccination are fully protected,’ she said.
 
Another unknown is the length of time for which immunity against COVID lasts, and whether vaccination or infection provides longer-lasting protection.
 
Dr Marsh Fox and Professor Kelleher believe infection can typically give longer-lasting immunity, whereas Associate Professor Griffin said immunity following COVID infection does not always occur, and that the vaccines have been designed to give more ‘potent immunity’.
 
Professor Godfrey also believes vaccine-induced immunity would likely extend for a longer period than infection-induced immunity, but there is not enough evidence to know for certain.
 
‘One of the shortcomings of the way these trials are being expedited is while we know a lot about how a lot of people respond to the vaccines in the timeframes we’re looking at, we simply cannot say if they will still have immunity in a year’s time,’ he said.
 
But regardless of whether any of the vaccine candidates will eventually allow Australia to reach herd immunity, one thing about which Professor Godfrey is certain – and with which Associate Professor Griffin and Professor Kelleher agree – is that pausing any rollout to wait for a more ‘efficacious’ vaccine would be unwise.
 
‘I certainly wouldn’t be writing off the AstraZeneca vaccine yet, especially since we don’t have an option of saying we want the Pfizer, or any other vaccines instead,’ Professor Godfrey said.
 
‘While we have an agreement in place with Pfizer for 20 million doses, this is dependent on importation and it’s likely only three million will have arrived by June.
 
‘It’s probably going to be the AstraZeneca vaccine or just wait; and “just waiting” could leave us very vulnerable, especially if we get another major wave.’
 
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