The organizers are already recruiting; in terms of participants, they are focusing on people aged 50 years and above who have not yet received a COVID-19 vaccine.
The researchers said they will also be looking at the impact of the interval between doses on immune responses.
The study, which will last for 13 months, is being run by the UK’s National Immunization Schedule Evaluation Consortium (NISEC) and is backed by £7m (US$9.5m) UK government funding. The idea is to hopefully provide for flexibility in COVID-19 vaccination delivery.
UK deputy chief medical officer and senior responsible officer for the study, professor Jonathan Van-Tam, said: "Given the inevitable challenges of immunizing large numbers of the population against COVID-19 and potential global supply constraints, there are definite advantages to having data that could support a more flexible immunization program, if needed and if 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.”
Matthew Snape, associate professor in pediatrics and vaccinology, University of Oxford, and chief investigator on the trial, said it “could [also] provide clues as to how to increase the breadth of protection against new virus strains."
What’s involved?
The COVID-19 Heterologous Prime Boost study (Com-Cov) will recruit over 800 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.
It will test a first dose of the Oxford-AstraZeneca vaccine followed by boosting with either the Pfizer vaccine or a further dose of the Oxford-AstraZeneca vaccine, or a first dose of the Pfizer vaccine followed by boosting with either the Oxford-AstraZeneca vaccine or a further dose of the Pfizer one.
Two different dosing schedules will be evaluated in the trial: at a four-week interval for an early interim data readout and at a 12-week interval for comparison to current UK policy.
Using blood samples collected from the trial volunteers, the study will monitor the impact of the different dosing regimens on participants’ immune responses and for any additional adverse reactions to the new combinations of vaccines.
Professor Andrew Ustianowski, national clinical lead, NIHR COVID vaccine research program, said: ‘We need people from all backgrounds to take part in this trial, so that we can ensure we have vaccine options suitable for all.”
The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) would formally need to assess the safety and efficacy of any new vaccination regimen, however, before it would be rolled out to patients.
Combining vaccines 'likely to be safe'
Commenting earlier this month on the idea of combining vaccines in a regimen, Prof Helen Fletcher, professor of immunology at the London School of Hygiene & Tropical Medicine, said:
“We are fortunate to have a first generation of COVID-19 vaccines that are highly effective. For many diseases, such as HIV, TB and malaria, the immune response to one vaccine is not sufficient to provide a high level of protection so the next logical step is to combine two different vaccines delivering the same antigen in a heterologous prime-boost regimen.
“In a heterologous prime-boost, we would give the spike protein using one vaccine platform and then present the same spike protein using a different vaccine platform – this could give a much stronger immune response to the spike because the second vaccination isn’t limited by any anti-vector immune response.
“Heterologous prime-boost regimens would be an important strategy to explore in clinical trials if the first generation of COVID-19 vaccines had been weakly protective, as combining vaccines could boost the level and duration of efficacy. Where efficacy is already >90% there is little advantage to pursuing a heterologous prime-boost regimen, although if heterologous boosting extended the duration of efficacy, it would be worthwhile. Based on previous studies which combine different vaccine types, a combination of the AstraZeneca and Pfizer vaccines is likely to be safe, but it’s important that this is tested in the context of a clinical vaccine trial.”