UK trial shows ‘mix and match’ COVID vaccine combinations deliver outstanding results

A person wearing blue gloves prepares a syringe with vaccine.

Jeremy Lasek, PHAA 



While the eyes of the world have been on England this week as it became the first nation to lift most of its COVID-19 restrictions, health experts are also keenly watching the results of clinical trials, effectively ‘mixing and matching’ vaccine schedules.

Given the current situation in the UK with the seventh highest death toll in the world (128,823) and around 46,000 new COVID-19 cases a day (21 July), the success of the vaccination roll out is seen as the best hope of achieving the levels of herd immunity needed for a return to life as normal.

The UK’s vaccination program has been applauded for its speed and agility so far. Indeed, the UK has outstripped much of the world with 88% of its adult population having received at least one vaccination dose, and more than 68% have had the two doses (21 July).

COVID-19 vaccine trials

At the recent PHAA National Immunisation Conference we heard about world-first trials underway in the UK to explore the effectiveness of alternating different COVID-19 vaccines.

Chief Investigator of the trial, the University of Oxford’s Professor Matthew Snape, told the conference the COVID-19 Heterologous Prime Boost Study was evaluating four different combinations (or a mix and match) of prime (initial) and booster (follow-up) vaccinations: Oxford-AstraZeneca (AZ) prime and booster; Pfizer prime and booster; Oxford-AZ prime with a Pfizer booster; and vice-versa.

Professor Snape said the trial, backed by government funding was commissioned even before the first vaccines were being rolled out in England.

‘The task we were given was to look for and give greater flexibility in the delivery of the vaccines in the UK in case of disruption to supply. Would we be able to switch over to the other one mid-schedule?’ Professor Snape asked.

‘So, if you had a first dose of the Oxford-AstraZeneca vaccine and that was no longer available to you, would you be ok if your second dose was the other available vaccine, the Pfizer vaccine?’

To study the impact of the intervals between doses on immune responses, two trials were initiated over 4 and 12 weeks. The trials involved 830 volunteer participants, aged 50 and above, from eight locations across England.

Trial results

The results of the trial have produced some remarkable results but Professor Snape emphasised that all combinations of the vaccines available produced excellent protection against COVID-19.

The headline finding is that the ‘mix and match’ approach to vaccination may result in an additional, more ‘robust’ protection against the COVID-19. People who received the AZ vaccine first, followed four weeks later by a Pfizer dose, produced antibody levels nine times higher than those given two back-to-back doses of the AZ vaccine.

Alternatively, those involved in the trial who were given Pfizer first and AZ second had antibody levels five times higher than those who received two doses of the AZ vaccine.

Two doses of the Pfizer vaccine produced the highest antibody levels, but the T-cell response was higher in people receiving the combination of vaccines.

‘You have to remember, AZ is a highly effective vaccine against disease alone, and indeed is 92% effective against the Delta variant when it comes to severe disease and hospitalisations,’ Professor Snape said.

Further trial results are due shortly testing the mix-and-match approach with a 12-week gap between the first and second doses, the current schedule in the UK.

Further studies

Beyond that, another study, called Cov-Boost is currently testing combinations of booster shots for people who’ve received either two doses of AZ or Pfizer vaccines.

‘We are now planning ahead for the third dose booster, remembering our highest at-risk groups were vaccinated from December, and the concern is to avoid a third wave of hospitalisations this next winter.’

Professor Snape said consideration is also being given to whether the third dose of a COVID-19 vaccine could be given alongside the annual influenza vaccine.

That will be the subject of a further study involving 745 adults aged 18 and over who usually receive an annual flu vaccination.

Professor Snape told the conference, the findings of these ground-breaking trials could add much-needed flexibility to vaccination programs around the world.

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