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Mixed Oxford and Pfizer vaccine schedules shows robust immune response against COVID-19

Alternating doses of the Oxford/AstraZeneca and Pfizer vaccines generate robust immune responses against COVID-19, an NIHR supported study has found. The Com-COV study is led by the University of Oxford and run across eight NIHR sites in the UK.

Newly published early results report that both ‘mixed’ schedules (Pfizer/BioNTech followed by Oxford/AstraZeneca, and Oxford/AstraZeneca followed by Pfizer/BioNTech) generate high concentrations of antibodies against the SARS-CoV2 spike IgG protein when doses were administered four weeks apart.

This means all possible vaccination schedules involving the Oxford/AstraZeneca and Pfizer 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 results show that when given at a four-week interval both mixed schedules induce an immune response that is even better than that seen after the standard schedule of the Oxford/AstraZeneca vaccine. The investigators would like to thank the participants that made this important study possible.

“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.”  

Of note is that the order of vaccines made a difference, with an Oxford/AstraZeneca then Pfizer/BioNTech schedule inducing higher antibodies and T-cell responses than Pfizer/BioNTech then 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 schedule, and the highest T-cell response from Oxford/AstraZeneca followed by Pfizer.

Professor Andrew Ustianowski, NIHR Clinical Lead for 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."

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) Joint Committee on Vaccination and Immunisation (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.”

In May, researchers reported preliminary COMCOV 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 NIHR supported sites, including Oxford, London, Birmingham, Liverpool, Nottingham, Bristol and Southampton, to evaluate the four different combinations of prime and booster vaccination.

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

Those interested in finding out more about vaccine studies and volunteer to be contacted about taking part in trials can sign-up to the NHS COVID-19 Vaccine Research Registry.