What to make of the news this morning that Oxford University is to ask for volunteers to take part in a trial to ‘mix and match’ the Pfizer and AstraZeneca vaccines? Researchers will ask for 820 volunteers, all over 50 years old, who will be given two shots of a vaccine, two weeks apart. Some will receive AstraZeneca followed by Pfizer, some the other way around and some — the control group — will be given two doses of the same vaccine.
Britain has set itself apart from the EU, not just in the speed and extent of its vaccine procurement programme but also for its willingness to experiment. For example, while other countries have stuck rigidly to the manufacturers’ recommendation that the Pfizer vaccine be given in two jabs, 21 days apart, in Britain the second jab is being delayed for up to 12 weeks.
There are two sides to this approach. On the one hand, it risks undermining public confidence — when you have the government diverging from manufacturers’ guidance it isn’t going to help convince that proportion of the population which is reluctant to get vaccinated at all. On the other hand, we may discover a more effective vaccination strategy. It isn’t that Pfizer has experimented with different vaccination intervals and hit upon 12 weeks as optimum. That was the only gap tested in the Phase 3 trials of the Pfizer vaccine. There is no data on any other interval, but that doesn’t mean that three weeks is optimum. As for the AstraZeneca vaccine — as I wrote here the other day — we do have data for different intervals, which suggests a gap of three weeks or more is more effective.
The leader of the Oxford study into mixing vaccines, Matthew Snape, didn’t exactly do his best to sell the study on this morning’s Today programme when he first described the practice as a means of dealing with shortages of one particular vaccine. That made it sound like a desperate measure to keep the vaccine programme rolling along as fast possible. Public Health England has previously said that it might give some people different doses but only in exceptional circumstances — which could add to the impression that mixing vaccines is sub-optimal.
In fact — and this is a far better justification for the Oxford study — there is a body of evidence suggesting that in some cases giving two doses of different vaccines (known as a heterologous prime-boost) is more effective than giving two doses of the same vaccine (a homologous prime-boost). This was found to be true, for example, in a study into tuberculosis vaccination of calves and also to herpes vaccination in mice. A review of the evidence was published in the journal Current Opinion in Immunology in 2009.
But one thing is for sure. In vaccination programmes, public confidence counts for a huge amount. If we cannot persuade people to take the vaccine — and there is a big problem in some Bame communities with the Covid vaccinations — then we risk making the vaccination programme a lot less effective. One GP, Dr Rosie Shire, recently described the decision to stretch the gap between doses of the Pfizer vaccine as an ‘unregulated and unlicensed trial’.
It is good, then, that the practice of giving people two different doses is to be tested in a group of volunteers in an organised trial rather than simply being sprung upon the population. It won’t be the only such trial: AstraZeneca is already investigating the possibility of mixing doses of its vaccine with the Russian Sputnik vaccine. If successful, either if these experiments could greatly improve the speed and effectiveness of vaccination programmes, something which will be hugely important when the vaccination effort moves on to the developing world.
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