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Mixing COVID vaccines could result in stronger immune response


Anastasia Tsirtsakis


28/07/2021 4:51:23 PM

New research suggests mixing one dose of AstraZeneca with either Pfizer or Moderna could be beneficial. Is it something Australia should consider?

Pfizer and AstraZeneca COVID-19 vaccines.
New research has suggested mixing COVID vaccines could induce a stronger immune response than two doses of the same candidate. (Image: AAP)

The study conducted in Germany and published in Nature Medicine involved 216 volunteers. Fifty-five received two doses of AstraZeneca’s viral vector vaccine, 64 received two doses of an mRNA vaccine, and 97 received a combination of one AstraZeneca dose and an mRNA booster shot.
 
The findings revealed that one shot of AstraZeneca followed by a shot of either Pfizer or Moderna resulted in a stronger immune response than having two doses of AstraZeneca.
 
The study also found that the combination gave an equally strong, or stronger, immune response than two doses of an mRNA vaccine.
 
The findings are consistent with other similar studies, including Oxford University’s Com-COV trial. Involving more than 800 volunteers, it found those who received a mix of AstraZeneca and Pfizer generated a strong immune response against the virus.
 
However, the order of vaccines made a difference, with AstraZeneca followed by Pfizer ‘inducing higher antibodies and T-cell responses than Pfizer followed by AstraZeneca’.
 
Professor Dale Godfrey, Immunology Theme Leader at the Doherty Institute, told newsGP there are several other studies investigating the heterologous approach, due in part to AstraZeneca’s slightly weaker efficacy, as well as concerns around thrombosis with thrombocytopenia syndrome (TTS).
 
While it is not yet clear why the combination induces a greater immune response, he says there is some speculation.
 
‘One of the potential concerns with AstraZeneca, and it’s the same for the other vector vaccines, is that they have a viral vector that’s an adenovirus vector. So, basically, they put a part of the SARS-CoV-2 virus – the spike – into a different virus, an adenovirus,’ Professor Godfrey said.
 
‘The problem is that you make an immune response not only against the SARS-CoV-2 spike, which is what the vaccine’s intended to do, but you also make an immune response against the whole adenovirus vector – and that makes sense, because that’s also foreign.
 
‘But the next time you get the adenovirus vector, your immune system may detect the whole virus vector and clear it before the vaccine really has a chance to boost the spike response. So you’re basically making the vaccine less efficient on reinjection.
 
‘But if you come along with an mRNA vaccine as the boost, all you have is the spike, and so that really focuses the parts of the first response just on the spike and therefore, you get a very pronounced response against the spike, which is the part of the virus that we want to make a response against.’
 
With the spread of the more infectious Delta variant resulting in reduced vaccine efficacy, some experts have proposed that combining vaccines could help improve immune responses, particularly when using AstraZeneca.
 
However, Professor Godfrey says it is still not known whether the approach will prove more protective against variants.
 
‘When you’re looking at hospitalisations and severe disease, they’re all very good. But it’s generally considered that the mRNA vaccines provide the most robust protection across the variants, and from studies such as this one, the heterologous approach is likely to provide better protection against the variants than straight AstraZeneca prime and boost,’ he said.
 
‘I don’t think that has yet been carefully examined. [But] typically the higher the amounts of antibody and T cells, so the stronger the immune response, the more effectively you can handle the variants. So it’s likely that heterologous vaccination will help protect against the variants.’
 
Professor Godfrey says mixing vaccines is not new. For example, Australians aged 65 and over are more likely to receive an enhanced influenza vaccine, which is essentially a booster.
 
‘It has been done. There’s nothing inherently risky about the approach, other than it’s just less extensively tested in the context of COVID,’ he said.
 
However, the UK study did find that mixing viral vector and mRNA vaccines can also lead to an increase in mild to moderate side effects.
 
This increase was not noted in the German study, but it did find that following a dose of AstraZeneca with an mRNA booster resulted in a similar reaction to having the second of two mRNA doses, which can leave recipients feeling unwell for a few days.
 
Professor Godfrey said the disparity between the studies could be due to the interval between doses.
 
‘In the UK study … the boost vaccine was given four weeks after the prime. Whereas in the German study, the boost was 9–12 weeks later, and so there’s been a bit more time for the immune system to settle down,’ he said.
 
‘And therefore, maybe the reactogenicity on the boost is a bit more moderate because the immune system isn’t quite so revved up when that boost is administered.
 
‘But I don’t think it’s dramatically different, and I think in the big picture of things, these reactions are not the primary concern here; the primary concern is to make sure that people get good, robust immune responses and that they want to avoid any risks of the more serious side effects.’


Several countries have already started mixing COVID vaccines with the view to increase the speed of uptake, including Germany, Italy, Canada, South Korea, Thailand, and the United Arab Emirates.
 
It was also authorised by Public Health England in January, while the US Centers for Disease Control and Prevention has permitted mixing vaccines in ‘exceptional circumstances’, but only for mRNA varieties.
 
So, given the Australian Government recently secured an additional 85 million Pfizer doses and 25 million doses of Moderna, could the mixed approach to COVID vaccination be taken locally?
 
Professor Godfrey says it is likely inevitable.
 
‘AstraZeneca is gradually being more limited, although at the moment it is still playing an important role, particularly while we have this Delta virus outbreak,’ he said.
 
‘[But] I think once we have access to enough Pfizer vaccines that people will be looking and expecting to get a Pfizer, or other mRNA vaccine, boost.
 
‘I don’t know – but ultimately, I think it’s inevitable that we will be getting a different vaccine, whether it’s later this year or next year as a boost. That’s assuming that boosts are required.
 
‘Regulators are always reluctant to switch from what’s been tested in the clinical studies, but the studies are coming out now, and this one we’re talking about today is another example … and there were no problems; they got good robust immune responses – all the things that you really desire from a vaccine.’
 
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Dr Gobind Singh Duggal   29/07/2021 9:17:11 PM

I think if one has first AZ vaccine without any side effects, the 2nd dose of AZ vaccine would be lot sfaer than unkown side effects ofrom Pfizer vaccine on that person, for benifit of little more protction from Covid, I would stick to same 2nd dose of vaccine