Disquiet is growing over the UK’s decision to change the dosing regimens for the two coronavirus vaccines it has approved, as experts question the justification for the long period between the first and second jabs.
When the decision to administer the two doses up to three months apart was unveiled on Wednesday, observers were puzzled.
Late-stage trials that in November had yielded overall efficacy of 70 per cent and 95 per cent for the Oxford/AstraZeneca and BioNTech/Pfizer vaccines had focused on 28- and 21-day intervals between doses, respectively.
UK health authorities argue that broader, if slightly lower, immunity for more people, rather than clinical trial level efficacy for a smaller number, is needed to counter the rapid surge in cases that has put significant pressure on hospitals across the country.
Late on Thursday, the UK’s chief medical officers said they were confident “that the first dose of either Pfizer or [AstraZeneca] vaccine provides substantial protection within two to three weeks of vaccination for clinical disease, and in particular severe Covid disease”.
Justifying their decision, they added that vaccine shortages were “a reality that cannot be wished away”.
But the UK’s approach remains unusual.
Moncef Slaoui, head of Operation Warp Speed, the US government’s vaccine procurement and development programme, warned that it appeared to be founded on “more of a conceptual observation” because it was not based on data from large-scale trials.
Mr Slaoui said it was “important” to use vaccines as studied and to use one clear efficacy figure. Echoing his remarks, Pfizer on Thursday hit out at the UK decision, saying there was no data to support a longer interval between doses.
Jonathan Stoye, a virologist at The Francis Crick Institute, said doubts on dosing and efficacy “would likely lead to delays in the approval process and requests for more data from the regulators” under more normal circumstances. But he said the UK move could be regarded as a “pragmatic” decision amid rapidly rising caseloads.
Oxford and AstraZeneca said the first dose of their vaccine gave the full 70 per cent measure of protection and that the second dose simply increased the duration of that response. Both insisted in the wake of the UK approval that the dosage change was based on robust foundations.
Andrew Pollard, Oxford’s chief investigator on the trial, said the UK study had involved dosing intervals of between four and 12 weeks and in some instances even longer. The periods between doses in the trials run in Brazil and South Africa were smaller — between four and seven weeks, and about four weeks, respectively.
The UK Medicines and Healthcare Products Regulatory Agency, which approves vaccines, had examined all the data by country and dosing interval and “the overall message from this is that we have good protection with that dosing interval,” Prof Pollard added.
Pointing to evidence that leaving more time between doses often boosted an immune response, he said that currently the vaccine’s efficacy was 70 per cent but “there is this possibility with a longer dosing interval that the efficacy may be higher.”
Defending the transparency of their approach, Prof Pollard said: “All of the data are already published in the Lancet [medical journal] . . . We do have data from the point of three weeks after the first dose.”
Sten Vermund, the dean of the Yale School of Public Health, said the UK’s dosing decision was “an intriguing gamble”. He said it resembled “an open label trial” because the approach, while theoretically sound and empirically supported for other vaccinations, lacked specific large-scale evidence for Covid-19.
“I worship at the same altar we all do: randomised control trials, hopefully double blinded, for vaccine efficacy,” he said, referring to the gold standard in clinical research.
“But I’m also a pragmatist,” he added. “You don’t go into public health without expecting to adapt to circumstances as they evolve.”