Mind the gap: the evidence behind the government's Covid-19 vaccine dosing strategy

When the UK first suggested a 12-week gap between Covid-19 vaccine doses, it was seen as a gamble.

The decision was taken in December 2020, when the vaccine campaign was just kicking off, with an aim of giving as many people as possible some protection in the face of rising cases and uncertain supply.

Yet the policy was enacted on somewhat shaky ground – particularly for the Pfizer jab, which had not tested the longer interval in clinical trials.

So far, though, the gamble seems to have paid off, with a rip roaring vaccination programme, falling mortality rates, and increasing evidence backing up the move.

But this week – in an effort to speed up Britain’s vaccination rollout in the face of the delta variant – the Government announced that the gap between vaccine doses will be cut from 12 weeks to eight for all adults, for all of the jabs being rolled out across Britain. It follows a similar move closing the dosing gap for the over-40s taken last month.

So what is actually the optimum time to leave between doses for the three vaccines currently being used in the UK – Oxford University/AstraZeneca, Pfizer/BioNTech and Moderna?

Our Global Health team takes a look.

Oxford University/AstraZeneca

The manufacturers of this jab recommend that the second shot comes between eight and 12 weeks after the first.

This is a guideline the UK has followed, shifting from one end of the time period to the other depending on the situation around supply, the medical history of the individual, and the risk of infection.

But there is growing evidence that aiming for the latter end of this range does confer slightly greater protection on a population level.

According to trial data published in The Lancet in January, the AstraZeneca vaccine is 82.4 per cent effective at stopping infection when a second shot is given at least 12 weeks after the first. This figure drops to roughly 55 per cent if the second dose is administered within six weeks. This effectively suggests that the larger gap will ultimately prevent more infections across the population.

A more recent preprint, published in June, looked at the antibody responses of 30 people who received their second shot of an AstraZeneca jab later than intended. It found that those who saw a gap of 45 weeks had a significantly higher antibody response after their second dose.

In reality, though, no one is suggesting individuals wait that long to gain more protection - especially in the face of highly contagious variants.

According to data from Public Health England, one dose of either the Pfizer or the AstraZeneca vaccine is 31 per cent effective at preventing symptomatic disease from the now-dominant delta variant. This number rises substantially, to 80 per cent, after two doses – which is why UK authorities are pushing to cut the gap to eight weeks.

“It has become more important for people to have two doses sooner than with the 12-week interval we initially used,” Dr Peter English, former editor of the journal Vaccines in Practice, told The Telegraph.

He added that, in the face of delta, the “difference made by longer intervals decreases...a 12 week interval is better than a six-week interval, but perhaps not as much better”.

In a world facing delta but without political and supply limitations, Dr English “would probably go with a six-week interval, followed by a second booster dose (a third dose), six-12 months later”.

Dr Julian Tang, a clinical virologist at the University of Leicester, added that a shift from eight weeks to 12 will make little difference to how much a vaccine protects an individual. He warned current data around optimal intervals is “rather open ended”.

Pfizer and Moderna

The manufacturers of the Pfizer/BioNTech vaccine sounded the alarm when the government first announced a 12-week gap, warning there was no evidence to support it.

They instead recommend a three-week or 21 day gap between the first and second doses. Independent scientists were also concerned.

However, the UK’s spacing strategy was at least partially vindicated for this vaccine, too. A study from the University of Birmingham in May found that a 12 week gap for the Pfizer jab induced a 3.5 times greater antibody response among people over 80 compared to a three week gap.

The immune response is complicated, though, and the picture at the T-cell level, an important part of long-term immunity, was a bit more mixed. More work on this area is needed, the researchers added.

The same applies for Moderna, the other mRNA jab currently in use in the UK. Its manufacturers recommend a 28-day interval between doses, although the United States Centers for Disease Prevention and Control (CDC) is now allowing a gap of up to 42 days or six weeks in the face of supply and distribution constraints.

The British Society of Immunologists has said that delaying by a few weeks, or bringing forward by a similar time-frame, a second dose of the approved Covid-19 vaccines would be “unlikely to have a negative effect on the overall immune boost”, as long as it comes after the manufacturer's recommended interval.

However, Professor Anthony Harnden, deputy chairman of the Joint Committee on Vaccination and Immunisation, told Times Radio that while with AstraZeneca there is "absolutely no doubt" that a longer interval gives better protection, the picture is more complicated with Pfizer.

"It's quite clear from antibody T cells studies that you get much lower response, and poorer quality memory response, with the shorter interval - that's a four-week interval compared to an eight- to 12-week interval," he said.

"And the actual real data vaccine effectiveness studies show that there is a lower vaccine efficacy against symptomatic disease with shorter intervals compared to longer intervals. And then we got the modellers to look at this and, actually, the number of infections will rise if we reduce the dose. We just don't think there's any good short, or longer term gain by shortening the interval."

Overall, for anyone hoping to know the optimum day to schedule their second jab, it’s not an exact science – and it is also a work in progress, where the benefits of delaying or vaccinating more quickly depend on the context and availability.

But one thing is clear: the best way to protect yourself against coronavirus is to get both doses of the vaccine, within the recommended schedule, as soon as possible.

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