IN A bid to vaccinate as many people as fast as possible, the UK is taking an unorthodox strategy against covid-19. The country is eking out its vaccine supply by making most people wait three months to get their second dose of the two-shot regimen.
Both vaccines currently being used in the UK were intended to be given over much shorter timescales. Changing a medicine’s dosing schedule so dramatically is unprecedented, and some experts have branded it a dangerous gamble, putting lives at risk. But what does the evidence say?
The UK announced its approach on 30 December as it was battling a huge surge in covid-19 cases, partly driven by a new, more transmissible variant of the virus.
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This was the same day that the vaccine developed by the University of Oxford and AstraZeneca was approved, and it was immediately put on a timescale of up to 12 weeks between doses.
The UK government also announced that the interval between doses of the vaccine developed by firms Pfizer and BioNTech would be stretched to the same duration. By then, more than 600,000 people had already been given their first injection since the immunisation drive began on 8 December.
Many scientists were shocked by the move because it deviates from the dosing schedules intended in the vaccine trials: three weeks for the Pfizer/BioNTech vaccine and four weeks for the one from Oxford/AstraZeneca.
“A trial tells you that something works, so why would you change that?” says Stephen Griffin at the University of Leeds, UK.
The approach makes most sense for the Oxford/AstraZeneca vaccine because between the doses. Some people in the trials ended up getting their second shot up to 12 weeks after the first, and the vaccine’s effectiveness at preventing symptoms was 65 per cent in this group, compared with 53 per cent in the rest.
“We had to get over ourselves and take a pragmatic view. We are in an emergency”
The numbers involved were small, though, with only about 1800 people getting a delayed second dose. The participants also weren’t randomised to the different schedules, so this wouldn’t normally be seen as good enough evidence to support such a major change to dosing.
The move to delay the second shot was even more surprising for the Pfizer/BioNTech vaccine, for which all participants in the trials got their second dose after about three weeks. Pfizer and BioNTech say that two doses of its vaccine are required to provide the highest protection against the disease.
There is some evidence to support the change. In a , the UK’s chief medical officers said that the Pfizer/BioNTech vaccine’s trial shows a good level of protection even before the second dose is administered. The trial results indicate that the efficacy was 89 per cent from 15 days after the first dose. The vaccine has been found to offer 95 per cent protection from covid-19 overall, after both doses are given.
Data from a third vaccine, developed by biotech firm Moderna, showed a similar response after one dose, lasting for 15 weeks. The vaccine – like the Pfizer/BioNTech one – uses mRNA technology, and has been authorised for use in the UK but roll-out hasn’t yet begun.
The extended dosing schedule is deemed necessary by the UK government on public health grounds. “The great majority of the initial protection from clinical disease is after the first dose of vaccine,” the chief medical officers said in the letter to doctors, adding that immunising many people in the next three months is better than reaching half that number with two doses to give only slightly greater protection.
The only way that the longer schedule would lead to more deaths from covid-19 overall is if the delay more than halves the amount of immunity provided by the first dose, which is highly unlikely, says Stephen Evans at the London School of Hygiene & Tropical Medicine. “The numbers are so obvious.”
There are wider considerations, however. Leaving people with only partial immunity to covid-19 for many weeks could make the virus more likely to evolve vaccine resistance, England’s chief medical officer Chris Whitty has acknowledged, although he said it was “quite a small worry”. On the other hand, if vaccination roll-out were slower, more people would be exposed to infection, which also raises the chance that the virus evolves those critical mutations.
Another concern is that the extended dosing schedule could reduce the number of people who come back for their second shot. “The longer you leave it, the more time there is for people to forget,” says Deborah Dunn-Walters at the University of Surrey, UK, who is chair of the British Society for Immunology’s covid-19 task force. The change also raises ethical issues for the people who were given the first dose on the understanding that the second would follow three weeks later as per the trial data.
Overall, it is possible that the shift, and the controversy around it, will undermine confidence in the vaccine programme.
The scientific community is divided on the question of whether the UK strategy is a good one. The US Food and Drug Administration said in a statement that changes in vaccine administration “.
Legal issues
The answer may depend on whether you take the perspective of an individual or think of the whole population. Much of the backlash has come from the US, where overall public health has a lesser role in the medical system.
The US is also more litigious than the UK, says Evans. Someone in the US who catches covid-19 two months after their first vaccine shot could sue their doctor for delaying the second dose. But a doctor can’t be held responsible by infected people if they haven’t yet received a vaccine at all.
The British Society for Immunology’s covid-19 task force had initial concerns about the changes to the dosing schedule, and sought more information from England’s chief medical officer about the evidence. In the end, the society .
A separate criticism of the UK programme is that it supports giving people a different vaccine for their second dose from the one they received initially, in a mix-and-match strategy. Critics of the tactic include John Moore at Cornell University in New York, who has said that by doing this the UK is ““.
The move is less controversial than it appears. The UK has only said that vaccines could be mixed if someone was due to receive their second shot and there is no matching vaccine available, or if it is unknown which type they got initially.
Mixing the shots might even give better immunity. Previous work on other vaccines suggests that injecting someone with the same virus proteins in a different package provokes a stronger immune response. Known as a “prime-boost” strategy, it has been investigated in vaccines against HIV and malaria.
The debate rolls on, but the UK may not be an outlier for long. Last week, Denmark approved a delay of up to six weeks between the first and second shots of vaccine, and the German health ministry is , according to media reports. “There’s still quite a bit of debate, although I feel there’s a tilt towards a more flexible schedule,” says Leif Erik Sander at Charité – Berlin University of Medicine, who has argued for a delay between doses.
Even if the change to a delayed schedule isn’t ideal because it deviates from the time periods that were tested in the vaccine trials, the decision needs to be taken in the context of the pandemic, says Dunn-Walters. “We had to get over ourselves and take a pragmatic view,” she says. “We are in an emergency.”
