Administration of one dose of Pfizer / BioNTech vaccine followed by one of the Oxford / AstraZeneca vaccines (or vice versa) results in a higher frequency of mild to moderate side effects compared to the two standard doses of one or more the other vaccine, initial data from a key UK trial suggests.
The Oxford-led Com-Cov study is exploring the safety and efficacy of mixed-dose regimens as they are being considered in several countries – including the UK – to strengthen vaccine deployment programs that depend on unstable vaccine supply.
The trial involves 830 participants aged 50 and older, some of whom have underlying conditions. He tests four combinations: Oxford / AstraZeneca + Oxford / AstraZeneca; Oxford / AstraZeneca + Pfizer / BioNTech; Pfizer / BioNTech + Pfizer / BioNTech; and Pfizer / BioNTech + Oxford / AstraZeneca.
The first installment of data comes from the group of 463 participants who received their first and second doses (of any regimen) with an interval of four weeks. Participants self-reported symptoms within seven days of the second dose.
Overall, the two mixed dose regimens triggered more side effects. For example, fever was reported by 34% of patients who got Oxford / AstraZeneca followed by Pfizer / BioNTech; and 41% of those who received Pfizer / BioNTech followed by Oxford / AstraZeneca. Meanwhile, only 10% reported feeling feverish in the group that received the two doses of Oxford / AstraZeneca; and 21% reported the symptom in the group that received two doses of Pfizer / BioNTech.
Similar differences were seen for chills, fatigue, headache, joint pain, discomfort, and muscle pain. Overall, the side effects that occurred were short-lived and there were no other safety concerns, according to data published in letter form in The Lancet journal.
“These are the types of reactions we would expect with vaccines… and these are more or less the same types of reactions you see with standard schedules. It’s just that they happen more frequently, ”said Matthew Snape, chief investigator of the trial and associate professor of pediatrics and vaccinology at the University of Oxford.
Although the trial participants were aged 50 and over, real-world data suggests that younger age groups tend to have stronger reactions to vaccines, he noted. “We would expect this signal … of higher reactions in mixed calendars, to show up again, and [in] younger age groups, there could be even more reactions.
What these data suggest is that vaccinating a room full of nurses on the same day with a mixed schedule may not be ideal as it could trigger higher absenteeism rates the next day, he said. “In countries that are starting to think about using these schedules… they may need to be prepared for higher absenteeism rates.
“The reactions are often related to the stimulation of the innate immune response, so… that fundamental part of the immune response that sends an inflammatory signal – whether or not this is related to a truly enhanced immune response, we don’t know yet.” Snape said.
Data on the effectiveness of these mixed regimens in inducing an immune response are expected in the coming weeks. Trial investigators are also evaluating the impact of dosing participants 12 weeks apart.
Another study called Com-Cov2 will assess the impact of participants receiving the Oxford / AstraZeneca or Pfizer / BioNTech vaccine and then receiving the Moderna or Novavax vaccine for their second dose.