COVID-19 vaccine review finds ‘insufficient’ evidence for boosters

There is not enough evidence to plan widespread booster COVID-19 shots, a new review in The Lancet suggests.
 
The article ‘Considerations in boosting COVID-19 vaccine immune responses’ was published this week. Its authors include a group of scientists from international institutions such as the World Health Organization (WHO), the US Food and Drug Administration, the University of Washington, and the University of Oxford, among others.
 
They suggest vaccine efficacy against severe disease is so high that further doses ‘are not appropriate’ for now, even with the emergence of the more infectious Delta strain.
 
Lead author Dr Ana-Maria Henao-Restrepo, a medical officer at the WHO, said existing evidence is too weak to justify the booster programs, which have increasingly been a part of international efforts to counter the pandemic.
 
Israel was the first country to offer boosters widely, giving a third dose to citizens aged 60 and older from late July. Health authorities in both the United States and the United Kingdom have also announced plans for third booster shots in more vulnerable cohorts.
 
However, the authors strongly query the approach of targeting the entire adult population.
 
‘Taken as a whole, the currently available studies do not provide credible evidence of substantially declining protection against severe disease, which is the primary goal of vaccination,’ Dr Henao-Restrepo said.
 
The review authors acknowledge that a booster shot might work for people who are immunocompromised. However, as well as arguing there is not enough reliable data to confirm the efficacy of boosters, they suggest there is not yet enough evidence to provide reassurance about potential side effects from extra doses.
 
Instead, they argue for efforts to be focused on those who have not yet been vaccinated.
 
‘The limited supply of these vaccines will save the most lives if made available to people who are at appreciable risk of serious disease and have not yet received any vaccine,’ the authors write.
 
It is a stance that makes sense to Professor Peter Collignon, an infectious diseases physician who also works at the Australian National University Medical School.
 
‘They are not saying we won’t need boosters or that some people won’t need a third shot,’ Professor Collignon told newsGP. ‘But that’s different from saying everybody needs it and we need to do it now.’
 
Protection timing still unclear
While studies have suggested vaccine efficacy wanes over time, there has been much less information on the long-term impact on cutting severe disease and death.
 
The review article suggests other factors that could offer protection against severe disease are not yet fully understood.
 
‘Even if humoral immunity appears to wane, reductions in neutralising antibody titre do not necessarily predict reductions in vaccine efficacy over time, and reductions in vaccine efficacy against mild disease do not necessarily predict reductions in the [typically higher] efficacy against severe disease,’ it states.
 
‘This effect could be because protection against severe disease is mediated not only by antibody responses, which might be relatively short lived for some vaccines, but also by memory responses and cell-mediated immunity, which are generally longer lived.’
 
Similarly to The Lancet article, Professor Collignon suggests that vaccine supply would be better directed to developing countries that are behind with their vaccination programs.
 
‘The real issue is people who don’t get their first vaccine rather than over-promoting third vaccines,’ he said.
 
‘If we start getting third or even fourth doses to people in rich places, that’s people in Indonesia, Brazil, Africa who don’t get their first dose.
 
‘The more we don’t vaccinate the world, the more the chance of variants that may not respond to the vaccines and more uncontrolled spread.’
 
Confounding factors
The article also highlights the risks of confounding factors influencing studies that have already been carried out, with the potential to distort the results.
 
‘Apparently reduced efficacy among people immunised at the beginning of the pandemic could also arise because individuals at high risk of exposure [or of complications] were prioritised for early immunisation,’ the authors write.

‘Among vaccinated people, more of the severe disease could be in immunocompromised individuals, who are plausibly more likely to be offered and seek vaccination even though its efficacy is lower than it is in other people.’
 
Professor Collignon says existing studies have not yet proved the case for boosters, citing age as the biggest confounding factor in analyses so far.
 
‘You just can’t do this because you think it’s a good idea,’ he said.
 
‘You have to do the appropriate studies for the things that matter, [that protection against] death and hospitalisation really is dropping, and I don’t think that has been shown.
 
‘When I look at the data from Israel for instance, which is being reported as showing declining efficacy, it may for mild infection but for things that matter, which is dying and hospitalisation, if you adjust it for age groups, you are still getting 90% plus protection for all those age groups.’
 
Iceland, which has similarly high rates of vaccination, only recorded three deaths during its most recent – and largest ever – COVID wave, despite averaging around 100 cases per day for the month of August.


Israel was the first nation to begin offering booster COVID-19 vaccinations. (Image: AAP) 

Does fear play a role?
Professor Collignon believes the argument for booster programs is being clouded by emotion.
 
‘This is where fear drives your response, rather than acting on appropriate science,’ he said.
 
The authors of The Lancet article raise a similar point.
 
‘Careful and public scrutiny of the evolving data will be needed to assure that decisions about boosting are informed by reliable science more than by politics,’ they write.
 
‘Although the benefits of primary COVID-19 vaccination clearly outweigh the risks, there could be risks if boosters are widely introduced too soon, or too frequently, especially with vaccines that can have immune-mediated side effects.
 
‘If unnecessary boosting causes significant adverse reactions, there could be implications for vaccine acceptance that go beyond COVID-19 vaccines. Thus, widespread boosting should be undertaken only if there is clear evidence that it is appropriate.’
 
Booster plans for healthcare workers have already been mooted for Australia. The Federal Health Minister Greg Hunt has also indicated a widescale booster program is likely to take place, while the Federal Government’s placing of an order for 85 million further doses of Pfizer and 15 million ‘updated’ Moderna doses is another sign that booster programs are highly probable.
 
However, there have been no formal plans for booster programs announced for the wider population in Australia.
 
For Professor Collignon, the jury is also still out on any decision to offer boosters to healthcare workers who are likely to have had their immunisations early in the rollout.
 
‘I was vaccinated in March,’ he said. ‘But I would still like to see the data that says I need a booster.’
 
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