Certain mix-and-match vaccines enhances Covid protection, study finds

World’s first ‘mix and match’ Covid vaccine study finds combination of AstraZeneca and Pfizer jabs gives enhanced protection – but scientists say UK should stick to current schedule to keep rollout simple

  • Study trialled mixing AstraZeneca and Pfizer Covid jabs with four week wait
  • Researchers found AstraZeneca jab followed by Pfizer increased protection
  • But lead scientist warned jabs should only be mixed if there are supply problems 

Mixing and matching Covid vaccines may result in higher protection against the virus, a UK Government-backed study has found.

People who had been vaccinated with AstraZeneca’s jab initially and then received a top-up with Pfizer’s had nine times more antibodies than those who stuck to the UK vaccine.

Although antibodies are just one part of the immune response, the Oxford University researchers said the findings strongly suggested the approach could enhance immunity.   

However, Professor Matthew Snape, chief investigator of the trial, said the UK should stick to its standard dosing regimen because it was proving to work in the real world.

He warned there was a danger of complicating the hugely successful rollout, which has seen four-fifths of the adult population jabbed at least once.  

‘The default has to stay to what is proven to work,’ he told a press briefing this afternoon.

However, the findings opened the door for more flexible rollouts in countries with limited supplies, the scientists said. 

They will continue to monitor 830 participants in the trial to see how much protection the ‘mix and match’ strategy provides against Covid in the real world.

The top graph shows that two doses of Pfizer (green line) produces the highest antibody response out of any other vaccine combination, followed by one AstraZeneca jab and one Pfizer jab (orange line), one Pfizer and one AstraZeneca (blue line) and lastly two AstraZeneca jabs. The bottom graph shows that the mix of one Oxford jab and one Pfizer jab produces the most T-cells, followed by one Pfizer jab and one AstraZeneca injection, two Pfizer jabs and two Oxford vaccines

The latest study, published today in the Lancet, looked at the efficacy of either two doses of Pfizer, two of AstraZeneca, or one of them followed by the other. 

All second doses were given four weeks apart and the trial recruited 830 volunteers who were aged 50 and above.  All combinations worked well, priming the immune system. 

The Com-Cov trial found that AstraZeneca’s vaccine followed by Pfizer’s induced higher levels of antibodies and T cells than vice versa.

Both antibodies and T cells, a type of white blood cell, play a crucial role in defending against Covid.

The mix-match approach produced more antibodies than two regular doses of AstraZeneca’s, no matter which way round the jabs were given.

The early results from the Com-Cov trial, published today in the Lancet, looked at the efficacy of either two doses of Pfizer, two of AstraZeneca, or one of them followed by the other. 

All second doses were given four weeks apart and the trial recruited 830 volunteers who were aged 50 and above.  All combinations worked well, priming the immune system. 

It found: 

— AstraZeneca’s vaccine, followed by Pfizer’s, induced higher levels of antibodies and T cells than vice versa.

— Both antibodies and T cells, a type of white blood cell, play a crucial role in defending against Covid.

— The mix-match approach produced more antibodies than two regular doses of AstraZeneca’s, no matter which way round the jabs were given. 

 — The largest antibody levels were induced after two doses of Pfizer, and the highest T cell response was from AstraZeneca’s followed by Pfizer.

The largest antibody levels were induced after two doses of Pfizer, and the highest T cell response was from AstraZeneca’s followed by Pfizer. 

A higher proportion of people in the mix and match group suffered symptoms than the standard dosing cohort.

But the side effects were short-lived and mild.  Scientists will continue to monitor participants to see how long their protection lasts.

Professor Snape said the findings will give officials confidence that, if the UK’s Covid situation changes, then different dosing strategies are safe and highly effective.

The approach could be deployed if there are supply problems or someone has an allergic reaction to their first dose, for example. 

The data could also be useful for planning a potential vaccine booster regime, he added. 

But Professor Snape said while the data provides ‘reassuring evidence’ in these cases, he would not go as far as saying it was better to mix and match, despite the promising results.

The only vaccine schedules we have ‘direct evidence’ of protecting against infection, as well as the Indian ‘Delta’ variant, is two Pfizer jabs or two AstraZeneca jabs, he said.

‘The default should be sticking to vaccine schedules that we know work,’ he said. 

Professor Snape said the sample size of 810 was ‘not enough to pick up rare side effects’ that are one in 1,000 or one in 50,000, so that was one of the reasons why sticking to the default schedule was best.

But a mixture of vaccines was ‘better than none’ and people ‘need a second dose’, he said. ‘So if it is a case of no second dose or a mixed dose, then definitely get mixed,’ he said.

People will have different opinions of the data, but others will take his view of ‘what do we know works and what do we know about the safety’, he said.

He added that it was ‘more complicated’ to design a mixed vaccination schedule, but it has been done before with Ebola vaccines. 

Professor Snape noted that the four week schedule does not favour the AstraZeneca vaccine, as it is recommended that there is an eight to 12-week wait between those jabs.

The same researchers are working on an almost identical study that gives the same vaccination combinations but 12 weeks apart instead. They plan to publish this study in July.

The scientists are also examining different combinations of the Moderna and Novavax vaccines.

Professor Snape said he thinks there will be higher antibody and T-cell levels in all vaccine combinations in the results of this study.  

Deputy Chief Medical Officer Professor Jonathan Van-Tam said the data was a ‘vital step forward’ and shows that mixing vaccines ‘gives people protective immunity against Covid-19 after four weeks’.


Researchers found that one dose of the AstraZeneca vaccine, followed by one Pfizer jab four weeks later, gave the best protection out of the combinations the trialled

Booster jabs are NOT needed this autumn because two doses work so well against Indian variant, leading Oxford scientist says

There is no need to give Britons booster Covid vaccines this year because the current jabs work so well, a leading scientist claimed today.

Oxford University’s Professor Andrew Pollard, the lead researcher behind trials of the AstraZeneca vaccine, said sending the extra doses to developing countries where the most vulnerable are yet to receive any jab would be a better use of the UK’s supplies.

His comments came despite his team at Oxford finding that giving a booster to people months after they’ve been double-jabbed brings their immunity levels back to their peak.

The trial of 90 Britons showed for the first time that the third dose ‘significantly’ boosts antibody and T-cell counts, key indicators that the body is primed to defend against Covid. 

Two doses of the AstraZeneca jab have been shown to reduce hospitalisations by more than 90 per cent against both the Indian and Kent variants. But there is nothing in the data to show that a third jab would improve on that figure, Professor Pollard said.  

Last week, the former Health Secretary Matt Hancock promised the Government would set out plans for an autumn booster programme within the next few weeks.  

It comes as Professor Pollard said the UK is in ‘a very good position’ for restrictions being lifted. He is also leading an Oxford University trial of a new Covid vaccine that targets the South African ‘Beta’ variant.

He said: ‘Equally, they offer supportive evidence that the standard (non-mixed) JCVI recommendations for Covid-19 vaccination all produce highly satisfactory immune responses, for both main vaccines in use. 

‘Given the UK’s stable supply position there is no reason to change vaccine schedules at this moment in time.

‘The results for the 12-week interval, which are yet to come, will have an instrumental role to play in decisions on the future of the UK’s vaccination programme.

‘Our non-mixed (homologous) vaccination programme has already saved tens of thousands of lives across the UK but we now know mixing doses could provide us with even greater flexibility for a booster programme, while also supporting countries who have further to go with their vaccine rollouts and who may be experiencing supply difficulties.’

Professor Deborah Dunn-Walters, chair of the British Society for Immunology Covid-19 Taskforce, and professor of immunology at Surrey University, said it was ‘welcome news’ that all combinations of the jabs produced a ‘strong immune response’ against the virus.

She said: ‘While we look forward to more data on doses given 12 weeks apart, mixing these two vaccines not only appears to be safe but can give a higher immune response than the standard dosing regimens where first and second doses of the vaccine are the same.

‘While the findings of this study might allow for some flexibility and optimisation of the vaccination programme in the future, we continue to strongly encourage people to accept the offer of both doses of the vaccine within the current programme to ensure maximum protection from Covid-19.’

Professor Peter Openshaw, a professor of experimental Medicine, Imperial College London, noted that the ‘beautifully designed’ study found that the antibody responses were best with the two-dose Pfizer jabs, but the best T-cell responses were in those who had the AstraZeneca followed by Pfizer vaccines. 

He said: ‘Which of these is more protective in the long run remains to be determined, but in the meantime the study is reassuring that using a mixed vaccine approach is not only safe but can potentially give immune responses that are as good or better than those induced by single vaccine regimens.  

‘The next set of data from the 12 week dose interval is keenly awaited.’

Professor Paul Hunter, a professor in medicine at the University of East Anglia, said the findings are unlikely to affect the UK’s vaccination strategy, given that over 60 per cent of adults have had their second doses.

‘But this could have major impact on strategy for a booster campaign in the autumn,’ he said.

Professor Hunter said: ‘Those most at risk from the virus will most likely get a booster jab. 

‘People who have had a first course of AstraZeneca should probably be offered the Pfizer vaccine, or possibly Moderna or Novavax dependent on the future trial data from this study

‘People who had a Pfizer first course may not need an autumn booster but if they do then it probably does not matter much which vaccine they are offered.’

He added that the AstraZeneca jab will likely ‘perform somewhat better’ in the study with a 12 week gap between doses.

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