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Getting the Pfizer COVID-19 vaccine after AstraZeneca may result in better immune protection (preprint)

This article was published on
June 18, 2021

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A preprint study, which is not yet peer-reviewed, suggests that people whose second shot is the Pfizer/BioNTech vaccine after a first shot of the AstraZeneca jab may develop better immune protection than those who receive two AstraZeneca doses. Overnight, Canada has also changed its recommendations on mixing vaccines, and is now recommending that people who got the AstraZeneca vaccine as their first dose should get Pfizer-BioNTech or Moderna for their second shot.

A preprint study, which is not yet peer-reviewed, suggests that people whose second shot is the Pfizer/BioNTech vaccine after a first shot of the AstraZeneca jab may develop better immune protection than those who receive two AstraZeneca doses. Overnight, Canada has also changed its recommendations on mixing vaccines, and is now recommending that people who got the AstraZeneca vaccine as their first dose should get Pfizer-BioNTech or Moderna for their second shot.

Publication

Humoral and cellular immune response against SARS-CoV-2 variants following heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination.

Not peer-reviewed
This work has not been scrutinised by independent experts, or the story does not contain research data to review (for example an opinion piece). If you are reporting on research that has yet to go through peer-review (eg. conference abstracts and preprints) be aware that the findings can change during the peer review process
Peer-reviewed
This work was reviewed and scrutinised by relevant independent experts.

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Expert Comments: 

Professor Fiona Russell

Although mixing and matching vaccines allows flexibility in vaccination programs, especially in response to a shortage of supply, one vaccine being less effective than another, or rare side effects, such as TTS [thrombosis and thrombocytopenia syndrome] for the AstraZeneca vaccine, just because a booster of Pfizer following AstraZeneca gives enhanced immune responses doesn’t mean that this schedule confers enhanced protection. There is the potential that this may translate to longer-term protection but that is not known.

We already know that two doses of the AstraZeneca vaccine are similarly effective against hospitalisation for Delta and Alpha, and the original strain, compared with Pfizer/BioNTech. Therefore there is no need to implement mix and match schedules in Australia from an effectiveness point of view.

We also know that if TTS were to occur, it occurs mostly after the first dose, so for those people >50 years (including myself) who have had a first dose of AstraZeneca and now wondering what to do, it is even more unlikely for TTS to occur after a second dose of AstraZeneca. In fact, no TTS cases have occurred after the second dose of AstraZeneca in Australia. So, at this stage, there is no need for mix and match schedules for this reason in Australia right now.

In the future, it may be necessary to use mix and match schedules if one vaccine proves to be more effective against variants than another. We may need to get a booster with a different vaccine but we don’t know that yet.

Dr Anna Lene Seidler

This study has not yet been peer-reviewed, and thus, we should be cautious to use this study to immediately change COVID-19 vaccination policy from the current effective methods.

These are preliminary results from a small study where the researchers compare current vaccination methods of the AstraZeneca and BioNTech/Pfizer vaccines to a combination, using one dose of AstraZeneca and a booster 12 weeks later with one dose of BioNTech/Pfizer. Researchers saw an improved immune response for the vaccine combination, which is promising.

Other studies in the UK, Spain and Germany have found similar positive preliminary findings on the immune response. They also showed that combining AstraZeneca with BioNtech/Pfizer seems to be safe, as no serious side effects were observed.

But all of these studies were too small to show if the AstraZeneca/ BioNTech combination was in fact effective in preventing COVID-19. So the final verdict is still outstanding.

If shown to be effective in preventing people from getting sick with COVID-19 in larger studies, a BioNTech/Pfizer booster may be a good option for people aged under 60 who have already received a first dose of AstraZeneca.

Professor Raina MacIntyre

There are several studies now showing good boosting with a mixed schedule of AstraZeneca and Pfizer. This study shows better coverage of variants of concern with a mixed schedule, which is important because almost all the quarantine leaks that have caused outbreaks are variants of concern.

If we want to address hesitancy and get vaccination rates up, allowing this choice of a mixed schedule would help, but must be accompanied by securing additional doses. Hesitancy was high in the >50 group because of lack of choice, and this will now shift to the >60 group and those who received a first dose of AstraZeneca .

People over 50 are also at higher risk of death and severe complications from COVID-19 compared to younger people, so it is important this age group be vaccinated as soon as possible and that we do not leave hesitant older people in limbo while vaccinating younger people. We know a mixed dose schedule is effective, although it does increase non-serious, transient side effects like pain in the injection site and fever, as shown in another study.

Later this year we will have enough mRNA vaccines for all adults, so giving all people >50 the choice of a mixed dose schedule, as some countries are already doing, will help get vaccination rates up. Equity in access to vaccines and safe choices in vaccine schedule will help counter hesitancy.

Professor Bruce Thompson

The latest evidence to suggest that a second dose of Pfizer vaccine after a first dose of AstraZeneca is as efficacious, or indeed more efficacious, than having a second dose of AstraZeneca is very welcome indeed. Such evidence allows flexibility and options in the vaccine rollout. As always, this is preliminary data and will need peer review and further testing. However, it is very good news.

Nikolai Petrovsky

Mixing different vaccine technologies to get a better immune response is an old concept called heterologous prime-boost and has been used extensively in the field of HIV vaccines.  So, it should come as no surprise that an initial dose of the AstraZeneca adenovirus vaccine followed by a booster with the Pfizer mRNA vaccine results in a better response than two doses of the AstraZeneca adenovirus vaccine.

Part of the reason for this is that the adenovirus vaccine induces anti-vector immunity against itself, so each subsequent dose gives a much weaker effect – by substituting the mRNA vaccine you avoid this issue.

Plus, the data all suggest the mRNA vaccine is more potent than the adenovirus vaccine if put head to head. Hence it is likely that as some of the initial vaccines such as the AstraZeneca vaccine are shown to be ineffective or insufficiently safe, more and more people who have had initial doses of such vaccines will need to be boosted using other vaccines.

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