How efficacious is a single dose of a Covid-19 vaccine? This is perhaps the main question in British politics at the moment. The UK government believes that both the AstraZeneca and Pfizer vaccines, the two currently available in Britain, offer significant levels of protection after a single dose.
What do they mean by significant? They believe that clinical trial data shows that if you exclude the first fortnight after a single dose is administered to patients – ie when the body has not yet had time to mount an immune response – then very high levels of protection are offered against symptomatic Covid-19 over the subsequent fortnight. The data from Pfizer’s trial shows that that level of protection is about 90 per cent in the fortnight after the first fortnight. (The headline Pfizer trial rate of 52 per cent protection after a single dose, quoted in some reports, includes data from that first fortnight which the UK considers to be irrelevant.)
If this is the case, then a single dose of the vaccine does indeed provide extremely high protection against Covid-19. The other 10 per cent, meanwhile, are highly unlikely to suffer severe symptoms – they are likely to get a mild form of the virus. The probability of someone dying a fortnight after being vaccinated is, according to the data, in effect non-existent.
The question is what happens next: what happens in the eight weeks after that first month? Pfizer’s trial does not offer any data on this, as the company itself has pointed out. Nevertheless the government has extended the period of time between vaccine doses, from three to 12 weeks. It is banking on immunity lasting across that period.
That decision has been criticised by some. The chair of the British Medical Association, Chaan Nagpaul, last week criticised the decision in a letter seen by the BBC. Dr Anthony Fauci, the face of the US pandemic response, has said he is “not in favour” of the shift. And the World Health Organisation continues to recommend that a second dose is given three weeks after the first.
But it may be these countries, not Britain, who eventually shift. Canada is also prioritising the first dose of the vaccine, while Denmark has extended the possible window for a second dose to six weeks. Germany is also considering doing so, while the relevant French health authority has now recommended this strategy. These states and others may soon move from six weeks to 12 if the UK is correct that a high degree of protection is maintained throughout.
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Why are the British confident? First, data from the Moderna vaccine trial – which is very similar to the Pfizer vaccine – shows protection of about 80 per cent for all of those vaccinated by a single dose. The dataset is limited by its small size and non-random sample, as the UK government recognises, but the Moderna study measured the responses of trial participants from any time between one day and 15 weeks after being vaccinated. The high level of average protection is encouraging, given that it includes patients who only received a single dose for as long as 15 weeks.
But as in the Pfizer trial, there is no clear data that protection from the US-made vaccines will last for a second and third month. The median follow-up time in the Moderna vaccine was only four weeks. The Moderna finding is arguably not robust.
Nevertheless, as the UK has pointed out, there is no reason to suspect that protection will plummet after the first month. Data from the AstraZeneca trial suggests that protection lasts for up to 12 weeks. As the relevant Public Health England report puts it, “Exploratory analyses showed that increased immunogenicity [ie protection] was associated with a longer dose interval [than a few weeks]. Efficacy is currently demonstrated with more certainty for dose intervals from eight to 12 weeks.”
This dry scientific language obscures a major premise: that the UK can afford to spend 12 weeks administering a first round of doses before it starts administering the second round of longer-lasting booster shots. Britain is three weeks into that window, giving it another nine weeks before it needs to return to those vaccinated at the start of January.
The government committee that recommended this approach – the Joint Committee on Vaccination and Immunisation, an independent expert advisory body founded in 1963 –believes that the data from the AstraZeneca trial can be used to support a delayed approach for the Pfizer vaccine too. As they have put it: “There is currently no strong evidence to expect that the immune response from the Pfizer-BioNTech and AstraZeneca vaccines differ substantially from each other.”
No data has so far disproven the UK’s approach. Much was made last week of reports from Israel that single doses there had been “less effective than we had thought”, as one Israeli doctor put it. But the data is incomplete. Not enough time has passed. The data that has been provided is not unsupportive of the British approach. Most crucially, it shows that the vaccine does start to take effect a fortnight after being administered.
As one of the doctors connected to the study, Ran Balicer, said, “On day 14 post-vaccination, a drop of 33 per cent in positivity was witnessed in the vaccinated group and not in the unvaccinated… this is really good news.” And as another Israeli doctor, Ronni Gamzu, put it to Sky News: “I believe, truly believe, this is the beginning of the end because the vaccine creates the immune response.”
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If the UK is right in its approach, how many people can it vaccinate in the next nine weeks before it must start administering the second dose? In the past week (17 to 24 January) it administered 2.51 million first doses of the vaccine, a 41 per cent increase on the 1.78 million in the week before. That rate should continue to increase, with another set of vaccination centres opening this week.
At the current rate, the government is likely to have vaccinated the 15 million most at-risk Britons over the next three weeks – by mid-February, as the government plans. (Just shy of 6.6 million people had been given a first dose at the start of this week.) These at-risk groups account for 88 per cent of the fatality risk from Covid. Once a fortnight has passed, ie by the start of March, these groups should no longer be a fatality risk, which would greatly reduce the lethality of Covid-19.
If the rate of vaccination continues to increase – by, say, a further 40 per cent – then the UK government has a chance of vaccinating all 32 million people in the “priority” groups over the next nine weeks (all those over 50 and anyone younger who is deemed at risk). It is plausible that the UK will have vaccinated all of these groups by the anniversary of the first lockdown on 23 March. Life could – at least in Britain, which is vaccinating far more quickly than the rest of Europe – look more normal by April than currently feels possible.
That may seem extraordinary to say at a time when nearly 40,000 patients are in hospital with Covid across the country, nearly twice as many as during the first wave. But cases are down by a third from their peak in early January. Hospitalisations are levelling off and should soon decline.
The effects of the UK’s rapid vaccination over the past fortnight – 4.3 million have received their first vaccine dose in the past 14 days – are also yet to be felt. The immune response for these people is only now taking effect. While one in eight British adults have received a first dose of the vaccine, fewer than one in 20 have begun to build any protection. The level of actual protection across the UK is always a fortnight behind the number of people who have so far been vaccinated.
As bleak as the situation currently is, the benefits of the UK’s relatively rapid vaccine rollout should start to be felt in the coming weeks. Britain’s bold approach to vaccine dosing may yet be proven wrong, but it may become a global standard.
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