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COVID-19 vaccine study supports flexible intervals in mixed Pfizer and Oxford/AstraZeneca schedules

Published: 09 June 2022

A standard two-dose Pfizer-BioNTech or Oxford-AstraZeneca vaccine schedule showed a greater antibody increase when given at a 12-week interval, compared to a four-week interval.

These are the latest findings from the University of Oxford-led Com-COV study, supported by the National Institute for Health and Care research (NIHR), which has published a paper in the Lancet Respiratory Medicine.

In mixed schedules, only Pfizer-BioNTech followed by Oxford-AstraZeneca recorded a significantly stronger immune response in the 12-week versus 4-week interval groups, and only at 28 days following a second dose. This persisted to six months following the second dose.

No safety concerns were raised in the study of 730 participants, who were recruited across 8 NIHR-supported research sites.
The study supports flexibility in priming intervals (first and second doses) across all vaccine schedules studied – this can be helpful in countries where vaccine supply may be inconsistent.

Researchers running the study have reported results assessing the immune response and reactogenicity of two-dose vaccine schedules.

Matthew Snape, Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial, said: “This paper summarises data that have been made available to policy makers globally during the pandemic, providing vital information the impact of using short vs long intervals for a range of COVID-19 vaccine schedules.

“These data are relevant not only to COVID-19 vaccines, but also how future vaccines using mRNA and viral vectored platforms against different diseases may be best deployed.”

Professor Andrew Ustianowski, NIHR Clinical Lead for COVID-19 Vaccination Programme and Joint National Infection Specialty Lead, said:

“We continue to learn more about how we can get the very best out of the vaccine doses we have available globally. These latest findings from the Com-COV study show how we can get the most out of current vaccine supplies - something which is key when it comes to vaccinating those in Low-Middle Income Countries.

"It's thanks to the continued efforts of research staff and participants across the country which help to provide us with such important data, which shapes COVID-19 vaccine policy across the world."

Researchers reported other key findings from the study:
- T-cell responses decayed faster in the 12-week interval groups than in the 4-week interval groups.
- Extending vaccination interval from 4 to 12 weeks greatly reduced the likelihood of short-lived vaccine reactions in volunteers who - received Pfizer-BioNTech as a second dose regardless of the prime vaccine – by up to 80%.
- Prophylactic paracetamol had the greatest effect in reducing reactogenicity within the most reactogenic group – those receiving Pfizer-BioNTech followed by Oxford-AstraZeneca.

It is the first trial reporting randomised data looking at the effect of time interval and prophylactic paracetamol use for standard and mixed vaccine schedules using the Oxford-AstraZeneca and Pfizer-BioNTech vaccines.

Given concerns of increased reactogenicity with mixed 4-week vaccine schedules, participants were randomly assigned to receive advice to either take paracetamol soon after immunisation, and 3 further doses over the following 24 hours regardless of symptoms (prophylactic paracetamol) or take paracetamol if they became symptomatic (reactive paracetamol).

The Com-COV study first reported robust immune responses following mixed Oxford/Pfizer schedules in June 2021, and data from the study also informed the UK’s 2021 winter booster programme.

Professor Matthew Snape added: “As always we are indebted to the fantastic participants that took part in this study, and to the NIHR and Vaccine Taskforce for providing the funding and infrastructure support that made this possible.”

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