According to a guidance update on December 31, the UK government will allow people to be given doses of different COVID-19 vaccines under certain circumstances, despite a lack of evidence about the extent of immunity offered by such mixing. The issue has sparked criticism after a report in The New York Times quoted Cornell University virologist John Moore as saying there is “no data on this idea whatsoever” and that UK officials “seem to have abandoned science completely now and are just trying to guess their way out of a mess.”
The UK has so far authorized two COVID-19 vaccines for emergency use. Pfizer and BioNTech’s BNT162b2 was cleared in early December, with close to 1 million people having received their first dose, while AZD1222 from AstraZeneca and the University of Oxford was cleared last week, with the first doses due to be given starting January 4. Both vaccines consist of two-dose regimens given several weeks apart.
The UK government’s “greenbook” on vaccinations says “every effort” should be made to complete the immunisation course with the same vaccine. However, for people “who started the schedule and who attend for vaccination at a site where the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule.” The greenbook document noted that this mixing option is “preferred if the individual is likely to be at immediate high risk or is considered unlikely to attend again,” although it acknowledged that there is “no evidence on the interchangeability of the COVID-19 vaccines,” and that “studies are underway.”
‘Extremely rare’ occasions
Mary Ramsay, head of immunisations at Public Health England, suggested that situations in which the second dose of a vaccine would be different from the first were likely to occur only on “extremely rare occasions.” She added that in those circumstances it may be “better to give a second dose of another vaccine than not at all.”
Meanwhile, the new guidance differs from recommendations in the US, which has so far issued emergency-use authorisations to BNT162b2 as well as Moderna’s mRNA-1273, another two-dose vaccine given several weeks apart. The Centers for Disease Control and Prevention said authorised COVID-19 vaccines “are not interchangeable,” and that “the safety and efficacy of a mixed-product series have not been evaluated. Both doses of the series should be completed with the same product.”
Steven Danehy, a spokesman for Pfizer, noted that the company’s Phase III study findings, which demonstrated efficacy of 95%, relied on a two-dose schedule of BNT162b2. “While decisions on alternative dosing regimens reside with health authorities, Pfizer believes it is critical health authorities conduct surveillance efforts on any alternative schedules implemented,” he added.
Mix-and-match pilot trials
In December, the UK said that pilot trials were being planned to test whether a “mix-and-match” approach would offer better protection against SARS-CoV-2 infection. Specifically, rather than receiving two doses of the same vaccine, participants would receive one dose of either BNT162b2, which is mRNA-based, or AZD1222, which uses a replication-deficient chimpanzee viral vector, followed a few weeks later by a single dose of the vaccine they did not receive the first time around.
Meanwhile, controversy was sparked again recently when the UK decided to space out the dosing regimens for both BNT162b2 and AZD1222 in a bid to vaccinate more people with at least one dose of vaccine, rather than prioritising giving others their second shot. Pfizer has also called that decision into question, saying its two-dose regimen should be administered within the recommended 21-day interval as there are “no data” that a single jab offers sustained protection.