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World's first COVID-19 vaccine alternating dose study launches in UK

Published: 04 February 2021

The study will examine using different approved vaccines for the two doses, as well as different intervals between doses, and is backed by £7 million of government funding.

The world’s first COVID-19 vaccine study researching alternating doses of two approved vaccines - alongside different dosing intervals, begins today at eight research sites across England.

The NIHR supported study, referred to as the COVID-19 Heterologous Prime Boost study, or ‘Com-Cov’, will determine the effects of using a different approved vaccine for the second dose to the first dose, in addition to examining the efficacy of two different time intervals between doses.

Over 800 volunteers, aged 50-years-old and above, are expected to take part in the study at eight sites across England - including in Oxford, London, Birmingham, Liverpool, Nottingham, Bristol and Southampton.

Professor Andrew Ustianowski, NIHR Clinical Lead for COVID-19 Vaccination Programme and Joint National Infection Specialty Lead, said: “This is another exciting step forward in finding a variety of vaccine options for the UK and globally, for which the NIHR is integral to ensuring the participant recruitment for this study and the gaining of robust data on safety and effectiveness. 

"We need people from all backgrounds to take part in this trial, so that we can ensure we have vaccine options suitable for all. Signing up to volunteer for vaccine studies is quick and easy via the NHS COVID-19 Vaccine Research Registry."

Researchers will gather immunological evidence on different intervals between the first and second dose for a mixed-vaccine regimen against control groups when the same vaccine is used for both doses.

A same-dose regimen is currently implemented for the national COVID-19 vaccination programme, and there are no current plans for this to change. Anyone who has received either the Pfizer or AstraZeneca vaccination as part of the UK-wide delivery plan will not be affected by this study. They will receive their second dose from the same source and over the same 12 week interval.

Deputy Chief Medical Officer and Senior Responsible Officer for the study Professor Jonathan Van-Tam said: “Given the inevitable challenges of immunising large numbers of the population against COVID-19 and potential global supply constraints, there are definitely advantages to having data that could support a more flexible immunisation programme, if ever needed and approved by the medicines regulator.

“It is also even possible that by combining vaccines, the immune response could be enhanced giving even higher antibody levels that last longer; unless this is evaluated in a clinical trial we just won’t know.

“This study will be a promising opportunity to gain greater insight into how we can use the vaccines to stay on top of this nasty disease.”

Classified as an Urgent Public Health study by the NIHR, it is being undertaken by the National Immunisation Schedule Evaluation Consortium (NISEC) and the Oxford Vaccine Group, and is backed by £7 million of government funding from the Vaccines Taskforce.

Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, said:  “This is a tremendously exciting study that will provide information vital to the roll out of vaccines in the UK and globally.

“If we do show that these vaccines can be used interchangeably in the same schedule this will greatly increase the flexibility of vaccine delivery, and could provide clues as to how to increase the breadth of protection against new virus strains.”

The clinical study will monitor the impact of the different dosing regimens on patients’ immune responses, and whether this can be a viable route to increase the flexibility of the UK’s vaccination programme. It has received ethics approval, as well as approval from the Medicines and Healthcare products Regulatory Agency (MHRA) to commence.

Should the study show promising results, then the government may consider reviewing the vaccine regimen approach if needed, but only if proven to be safe and recommended by the Joint Committee on Vaccination and Immunisation (JCVI).


The study will initially have eight different arms, testing eight different combinations, but more products may be added:

  • Oxford/AstraZeneca and Oxford/AstraZeneca - 28 days apart
  • Oxford/AstraZeneca and Oxford/AstraZeneca - 12 weeks apart - as a control group
  • Pfizer/BioNTech and Pfizer/BioNTech - 28 days apart
  • Pfizer/BioNTech and Pfizer/BioNTech - 12 weeks apart - as a control group
  • Oxford/AstraZeneca and Pfizer/BioNTech - 28 days apart
  • Oxford/AstraZeneca and Pfizer/BioNTech - 12 weeks apart
  • Pfizer/BioNTech and Oxford/AstraZeneca - 28 days apart
  • Pfizer/BioNTech and Oxford/AstraZeneca - 12 weeks apart

The study will run for 13 months and patients will be recruited over the course of February via the NHS COVID-19 Vaccine Research Registry. Vaccinations are expected to start towards the middle of the month and initial results to be made available over the summer period.

If the study shows promising results, the MHRA would formally assess the safety and efficacy of any new vaccination regimen before it would be rolled out to patients.

Read more about NIHR COVID-19 research

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