BackLessons from the calculated risk behind UK’s Covid-19 vaccine rollout
With limited doses and soaring infections, British officials ripped up the rule book and delayed second shots
PremiumThe U.K.’s bold call to delay giving people a second dose of a Covid-19 vaccine has put it out in front in the race to inoculate the world against the disease.
Behind that decision: a group of 16 scientists who advocated a controversial move to overrule some vaccine manufacturers’ guidelines in order to get more first doses to more people.
The gamble appears to have paid off, with incoming data pointing to durable protection against falling ill after just one vaccine dose. But while some countries, such as Canada, have followed the U.K.’s lead, others including the U.S. are refusing, saying to do so could pose a risk to public health.
The decision by British authorities holds lessons for other countries as they fight to contain the pandemic. Indeed, the dosing debate raises difficult questions about whether some governments and their scientific advisers—for instance in the European Union, where vaccination campaigns are painfully slow—are being too risk averse.
In December, as a highly infectious Covid-19 variant ripped across the U.K., the group of scientists sitting on Britain’s Joint Committee on Vaccination and Immunisation concluded that delaying a second vaccine dose by up to 12 weeks could save lives.
“It would have been cowardly not to make that decision," said Adam Finn, an immunologist at the University of Bristol who sits on the JCVI. “We had a certain amount of vaccine and a certain amount of time."
Faced with a crisis, the U.K. government was open to doing things differently, said former British Prime Minister Tony Blair, an early advocate of delaying the second dose.
“The traditional way is ‘Well, we can’t be sure, we need more data, blah, blah, blah.’ OK, fine, but you know in a pandemic you’re losing lives and livelihoods every week," he said.
Altering rules on the fly risks stoking vaccine hesitancy if something does go wrong, said Jennifer Nuzzo, a professor and epidemiologist at the Johns Hopkins Bloomberg School of Public Health. “It is hard for me to imagine the U.S. making that decision," she said.
The U.K. has injected more than half its adult population with at least one shot of vaccine, putting it ahead of the U.S. and its European neighbors. Every adult is due to have received at least one shot of vaccine by the end of July. Daily deaths from Covid-19 have fallen to less than 100.
The speed of the vaccination drive means the U.K. economy is set to reopen over the spring and summer, with the Bank of England forecasting a boom later this year that will erase the losses of the pandemic by early 2022.
Still, some doctors harbor concerns about the country’s unorthodox approach, especially over the risks to the frail and elderly if immunity quickly fades after an initial dose. The delayed-dose strategy is also set to be tested in the coming weeks, as the rate of second doses is expected to fall while vaccine makers struggle to keep up with global demand and countries spar over who gets priority for scarce shots. So far 31 million Britons have received the first dose and just 4.1 million a second shot.
Britain’s Covid-19 response has been marked by a series of calculated gambles. Some went wrong. It initially held off on lockdown to allow the population to acquire some herd immunity. It now has the highest cumulative death toll from Covid-19 in Europe.
On vaccines, the bets have so far paid off. The government spent big and early to acquire the innoculations. U.K. regulators signed off on vaccines before anyone else. The country doled out a British vaccine developed by AstraZeneca PLC and the University of Oxford to its elderly population despite limited data available on whether it was effective in that age cohort.
The British government “took punts on things before there was data to support them," said Jeremy Brown, an expert on respiratory diseases who advised on the U.K. vaccine deployment.
Normally, vaccine doses are administered to the public in the same way that they were during clinical trials. To change dosing typically requires further real-world trials. Going into the pandemic, the JCVI had a record of recommending dosing changes without conducting more trials, arguing that money and time could be saved by cutting doses, with no effect on patient immunity.
For example, the JCVI changed the dosing recommendation for a widely used children’s pneumonia vaccine in 2006. In the U.S., three doses are given during a child’s first year of life, followed by a booster. In the U.K. only two are given in the first year, followed by a booster, with no effect on protection, say researchers.
Unlike immunization advisory bodies in other countries, “we can advise based on core principles where data are lacking," said Prof. Finn. In this case, the group was guided by how its members understood immune systems to work in practice.
Initially, as the trial data came in from shots developed by Pfizer Inc. and BioNTech SE, Moderna Inc. and AstraZeneca, the British government played it by the book: After quickly approving the Pfizer shot, it said there should be a three-week gap between injections.
When the trial data for the AstraZeneca vaccine was published at the end of November, scientists were flummoxed by an accidental finding. Volunteers who were given a half-dose shot followed by a full dose a month or more later had much better immune response than those who were given two full doses more closely together.
The error raised questions about whether the better immune response was down to the half dose or the time between shots. “That was what got us thinking," said Prof. Finn. The JCVI met in late December and after a short debate backed delaying the second dose, members say.
Though the 12-week dosing schedule was in line with what had been tested in AstraZeneca’s trials, Pfizer and Moderna said extending the dosing interval wasn’t something they would recommend, given that their vaccine trials looked at shorter, three-to-four-week intervals to determine efficacy. The U.S. Food and Drug Administration said delaying the second dose beyond the limits assessed in human trials poses a risk to public health.
In the EU, the Netherlands has extended the dosing interval to six weeks. Some other countries are considering a longer interval, but most are following the manufacturers’ recommendations, according to the European Center for Disease Prevention and Control.
In continental Europe, the rollout of AstraZeneca’s shot has been plagued by reports of side effects such as blood clotting—incidents that have proved rare in the U.K. The EU health agency has ruled it safe for general use.
In a letter to The Lancet medical journal in February, a group of physicians said that extending the dosing schedule for the Pfizer vaccine wasn’t supported by the data, since it relies on a new technology known as messenger RNA to deliver instructions to the body to trigger an immune response.
David Strain, a physician and instructor at the University of Exeter’s medical school in England, said he worries that vulnerable elderly people aren’t getting enough protection and their risk of infection might wane during the lengthy interval between doses.
Data so far have mostly provided support for the dose-extension call. Studies of vaccinated British healthcare workers, for instance, have shown a strong immune response after just one dose of vaccine. One analysis concluded it was comparable in potency to that obtained by previous natural infection.
“We find it quite reassuring," Susanna Dunachie, global research professor at the University of Oxford, told reporters during a recent briefing on that finding. “They are kind of getting the immune response from someone who’s had Covid already from that single dose."
This story has been published from a wire agency feed without modifications to the text.
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