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Mixed Oxford/Pfizer vaccine schedules generate robust immune response against COVID-19

Alternating doses of the Oxford-AstraZeneca and Pfizer-BioNTech vaccines generate robust immune responses against COVID-19, according to research in which UCLH played a key role.

In a paper published on the Lancet pre-print server, investigators in the Com-COV study 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.

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

UCLH dosed the first UK participants in the study, the first study in the world to look at alternating doses of COVID-19 vaccines.

Professor Vincenzo Libri, Director of the NIHR UCLH Clinical Research Facility and the UCLH Vaccine Research Centre, led UCLH efforts.

Professor Libri said: “We had good reason to think that this ‘mix and match’ approach would be effective, and we are pleased to report these results today. Using vaccines interchangeably would be very beneficial in giving people the protection they need – as it would allow flexibility in terms of the vaccine roll out. We are grateful to all participants who took part in our study, who have helped us take steps to get out of the pandemic.”

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, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, 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.”

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.”

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.

In April, the researchers expanded the programme to include the Moderna and Novavax vaccines. Assuming there are positive 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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