Mixed Oxford / Pfizer vaccine schedules generate robust immune response against 
COVID-19, finds Oxford-led study

Summary:


  *   Mixed schedules involving Pfizer-BioNTech and Oxford-AstraZeneca generate 
strong immune response against SARS-CoV2 spike IgG protein



  *   Doses administered four weeks apart; data for 12-week dose interval due 
soon.



  *   Immune responses differed according to order of immunisation, with 
Oxford-AstraZeneca followed by Pfizer-BioNTech generating the better immune 
response out of the two mixed schedules.



  *   Alternating doses of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines 
generate robust immune responses against COVID-19, according to researchers 
running the University of Oxford-led Com-COV study.

https://www.ox.ac.uk/news/2021-06-28-mixed-oxfordpfizer-vaccine-schedules-generate-robust-immune-response-against-covid


In a paper published on the Lancet pre-print server, they report that both 
‘mixed’ schedules (Pfizer-BioNTech followed by Oxford-AstraZeneca, and 
Oxford-AstraZeneca followed by Pfizer-BioNTech) induced high concentrations of 
antibodies against the SARS-CoV2 spike IgG protein when doses were administered 
four weeks apart.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014

This means all possible vaccination schedules involving the Oxford-AstraZeneca 
and Pfizer-BioNTech vaccines could potentially be used against COVID-19.

Professor Matthew Snape, Associate Professor in Paediatrics and Vaccinology at 
the University of Oxford, and Chief Investigator on the trial, said: ‘The 
Com-COV study has evaluated “mix and match” combinations of the Oxford and 
Pfizer vaccines to see to what extent these vaccines can be used 
interchangeably, potentially allowing flexibility in the UK and global vaccine 
roll-out.

‘The results show that when given at a four-week interval both mixed schedules 
induce an immune response that is above the threshold set by the standard 
schedule of the Oxford/AstraZeneca vaccine. The investigators would like to 
thank the participants that made this important study possible.’

Of note is that the order of vaccines made a difference, with an 
Oxford-AstraZeneca/Pfizer-BioNTech schedule inducing higher antibodies and 
T-cell responses than Pfizer-BioNTech/Oxford-AstraZeneca, and both of these 
inducing higher antibodies than the licensed, and highly effective ‘standard’ 
two-dose Oxford-AstraZeneca schedule. The highest antibody response was seen 
after the two-dose Pfizer-BioNTech schedule, and the highest T cell response 
from Oxford-AstraZeneca followed by Pfizer-BioNTech.

Professor Matthew Snape said: ‘These results are an invaluable guide to the use 
of mixed dose schedules, however the interval of four weeks studied here is 
shorter than the eight to 12-week schedule most commonly used for the 
Oxford-AstraZeneca vaccine. This longer interval is known to result in a better 
immune response, and the results for a 12-week interval will be available 
shortly’.

Deputy Chief Medical Officer Professor Jonathan Van-Tam said: ‘Today’s data are 
a vital step forward, showing a mixed schedule gives people protective immunity 
against COVID-19 after four weeks.

‘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 Andrew Ustianowski, NIHR Clinical Lead for the COVID-19 Vaccination 
Programme and Joint National Infection Specialty Lead, said: ‘We know that the 
Oxford-AstraZeneca two-dose schedule is highly effective and has helped to save 
many lives. The fact we now know it works well, in terms of immune responses, 
when combined with the Pfizer vaccine provides researchers with the valuable 
knowledge that these vaccines could be used flexibly for those yet to be 
vaccinated in the UK and globally.

‘It would have been impossible to discover these results without the 
willingness and efforts of research participants across the country. Yet again 
they have worked alongside researchers to help find an end to the spread of 
COVID-19.’

Previous Com-COV findings

In May, researchers reported preliminary Com-COV data revealing more frequent 
mild to moderate reactions in mixed schedules compared to standard schedules, 
however, these were short-lived in duration.

The University of Oxford is leading the Com-COV study, run by the National 
Immunisation Schedule Evaluation Consortium (NISEC) and backed by £7 million of 
government funding from the Vaccines Taskforce.

It aims to evaluate the feasibility of using a different vaccine for the 
initial ‘prime’ vaccination to the follow-up ‘booster’ vaccination, helping 
policymakers explore whether this could be a viable route to increase the 
flexibility of vaccination programmes.

The trial recruited 830 volunteers aged 50 and above from eight National 
Institute for Health Research (NIHR) supported sites in England to evaluate the 
four different combinations of prime and booster vaccination.

In April, the researchers expanded the programme to include the Moderna and 
Novavax vaccines in a new study, run across nine National Institute for Health 
Research supported sites by NISEC and backed through funding from the Vaccines 
Taskforce and the Coalition for Epidemic Preparedness Innovations.

The six new ‘arms’ of the trial each recruited approximately 175 candidates, 
adding a further 1070 recruits into this programme.

Both studies are designed as so-called ‘non-inferiority’ studies – the intent 
is to demonstrate that mixing is not substantially worse than not mixing – and 
will compare the immune system responses to the gold-standard responses 
reported in previous clinical trials of each vaccine.

If the studies show promising results, the Medicines and Healthcare products 
Regulatory Agency (MHRA) and the Joint Committee on Vaccination and 
Immunisation (JCVI) would formally assess the safety and efficacy of any new 
vaccination regimen.

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