The Com-Cov study, led by Professor Matthew Snape of Oxford University, has demonstrated that people can safely receive a first shot of the AstraZeneca vaccine followed by a second dose of the Pfizer jab over a four-week period – and vice versa.
Known as a heterologous prime-boost, this type of vaccination induces “high concentrations” of antibodies that target the spike protein which covers the outside of Sars-CoV-2, the study found.
This part of the virus is responsible for gaining entry to human cells, suggesting that mixing doses may be effective in better preventing infection.
The findings support the decision made by the likes of France and Germany to administer second Pfizer doses to those individuals who had initially received the AstraZeneca vaccine, which has been linked to rare blood clots in some recipients.
Countries which are facing a shortage of supplies will also be reassured that they can safely and effectively alternate the administration of different doses.
The immune response differed according to the order of immunisation, the Com-Cov study found. An AstraZeneca-Pfizer combination induced higher antibody and T-cell responses than the Pfizer-AstraZeneca combination.
Both of these mixed pairings also produced more antibodies than the standard two-dose AstraZeneca schedule, but the two-dose Pfizer regimen generated the highest antibody response overall.
A total of 830 people aged 50 and over, nearly half of whom had underlying health conditions, were recruited into the study. This group was split in two: 463 participants were given a mixed or standard dosing regime over 28 days, and 367 volunteers were vaccinated with the same combinations but over 12 weeks.
Prof Snape described the results as “an invaluable guide to the use of mixed dose schedules”.
However, he acknowledged the findings were specific to a four-week dosing interval, which is shorter than the eight to 12-week delay most commonly used for the 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,” he said.
Professor Jonathan Van-Tam, deputy chief medical officer for England, said the Com-Cov results were a “vital step forward”. But given the strength of the UK’s supplies, there is “no reason to change vaccine schedules at this moment in time,” he added.
The results of mixing doses of the AstraZeneca and Pfizer vaccines over a 12-week period will “have an instrumental role to play in decisions on the future of the UK’s vaccination programme,” Prof Van-Tam said.
“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.”
The administration of a third jab more than six months after the second shot raises the number of antibodies within the blood back to the same levels seen in the wake of double-dose vaccination.
The research also showed an increase in antibodies capable of neutralising the Alpha, Beta and Delta variants. But despite the findings, Professor Teresa Lambe, the senior author of the study, said “it is not known if booster jabs will be needed” given the high levels of protection against serious disease, hospitalisation and death already provided by the current vaccines in use.
Internally, ministers are working under the assumption that a third dose will be offered to the over 50s and clinically vulnerable, according to one Whitehall source.
In May, preliminary data from the Com-Cov study showed that mixing vaccine doses triggers more pronounced short-term side effects in people when compared to administering two shots of the same Covid jab.
The AstraZeneca-Pfizer and Pfizer-AstraZeneca combinations induced “greater systemic reactogenicity” than a standard two-dose schedule, the research found.
A larger percentage of participants who received two different doses over a 28-day period reported feverishness, chills, fatigue, headache, joint pain and muscle ache after their second dose, compared with people who were immunised with two shots of either the Pfizer or AstraZeneca vaccine.
These symptoms were mainly reported as “mild” by the recipients, but there was also an increase in “moderate” and “severe” side effects among those volunteers who received the heterologous prime-boost.
There was no hospitalisation following the onset of these symptoms, which were short-lived, with the mixed dosing schedule ultimately found to be safe.
A different branch of the study is also examining whether the Pfizer and AstraZeneca jabs can be safely mixed with the Novavax and Moderna vaccines, the latter of which has been approved for use in the UK.