A Blog by Jonathan Low


Jan 1, 2021

Why Some Countries And States Are Using 1 Rather Than 2 Dose Covid Injections

There is growing evidence that one dose injections of Covid vaccines from Moderna, Pfizer and Astra Zeneca may slow the spread of the virus long enough to enable countries facing massive spread to inoculate more people, thereby helping to stop the pandemic from worsening even as vaccines become available. JL

Benjamin Mueller and Rebecca Robbins report in the New York Times:

In a departure from strategies around the world, the British decided to give as many people as possible a first vaccine dose rather than holding back supplies for quick second shots, greatly expanding the number of people who will be inoculated. Delaying second vaccine doses  could double the number of people eligible for shots in the coming weeks and lighten the toll of the virus in countries facing years of vaccine shortages. “We’re talking about potentially vaccinating in the billions more people."

Britain became the first country to give emergency authorization to the coronavirus vaccine developed by AstraZeneca and the University of Oxford, clearing the path for a cheap and easy-to-store shot that much of the world will rely on to help end the pandemic.

In a departure from prevailing strategies around the world, the British government also decided to begin giving as many people as possible a first vaccine dose rather than holding back supplies for quick second shots, greatly expanding the number of people who will be inoculated.

That decision put Britain at the vanguard of a far-reaching and uncertain experiment in speeding up vaccinations, one that some scientists say could alleviate the suffering wrought by a pandemic that has been killing hundreds of people each day in Britain and thousands more around the world.

The global effort to accelerate vaccinations, coming as a new, more contagious variant of the virus is spreading, gathered steam in many places on Wednesday.

China said clinical trial results showed high efficacy for one of its vaccine candidates, an announcement that hastened the global rollout of hundreds of millions of doses of Chinese vaccines but was short on crucial details. Russia’s Sputnik V vaccine, long criticized for being introduced prematurely, also began use this week in Argentina, Belarus, Hungary and Serbia, the first other countries to begin injecting it en masse. And Argentina quickly followed Britain in authorizing the Oxford-AstraZeneca shot, with India expected to do the same soon.

Britain’s two moves on Wednesday — authorizing an easy-to-make, easy-to-deliver vaccine, and delaying second vaccine doses — offered one blueprint for how to ramp up inoculation campaigns that have so far been entangled in logistical and manufacturing problems there and in much of the West.

The Oxford-AstraZeneca shot is poised to become the world’s dominant form of inoculation. At $3 to $4 a dose, it is a fraction of the cost of some other vaccines. And it can be shipped and stored in normal refrigerators for six months, rather than in the ultracold freezers required by the Pfizer-BioNTech and Moderna vaccines, making it easier to administer in poorer and harder-to-reach areas.

Delaying second vaccine doses, too, could double the number of people eligible for shots in the coming weeks and eventually lighten the toll of the virus not only in Britain but also in countries facing years of vaccine shortages, some scientists said. While any one person may be better off with the full two doses, they said, society as a whole benefits if more people are given the partial protection of a single dose for the time being.

“We’re talking about potentially vaccinating in the billions more people in a given year, versus the alternative, which is to go with two doses and let them sit in a freezer,” said Michael Mina, an epidemiologist at Harvard who was one of the earliest proponents of delaying second doses. “There may be a trade-off for each of those individuals, but at the population level, you may end up saving many more lives.”

Still, other scientists believe that Britain overshot the available evidence, potentially leaving older people and health-care workers without the full protection of two vaccine doses amid dreadful wintertime surges. Britain did without the public meetings or voluminous briefings that have preceded American regulatory decisions. No trials have explicitly tested the long-term efficacy of a single shot.

And what limited evidence exists about the protection afforded by a single dose clashed with scientists’ fears that antibody responses would wane over time, potentially falling below a protective threshold.

“What is the longevity of any protective immunity for one dose, versus two doses?” said John Moore, a professor of microbiology and immunology at Weill Cornell Medical College. “Where’s the data?

Britain will delay the second, booster doses not only of the Oxford-AstraZeneca vaccine but also the Pfizer-BioNTech shot. That vaccine, in use in the country for several weeks, has been shown in clinical trials to have considerable efficacy after a single dose. Pfizer, though, cautioned on Wednesday that the single-dose efficacy data does not extend beyond when people receive their second shots, three weeks after the first. The company said that two doses “are required to provide the maximum protection against the disease.”

For Britain, where hospitals are overwhelmed by a deluge of cases of a new and more contagious coronavirus variant, the rollout of more vaccines offered a distant hope of a reprieve. Starting on Monday, the health service is preparing to vaccinate as many as two million people per week at makeshift sites in soccer stadiums and racecourses, though the first shipment will only include 530,000 doses.

Instead of administering the two vaccine shots within a month as was originally planned, clinicians in Britain will wait as long as 12 weeks to give people second doses, the government said. Doctors were scrambling on Wednesday to push back hundreds of appointments for second doses of the Pfizer-BioNTech vaccine and fill them with first-time recipients.

Clinical trials of the Oxford-AstraZeneca vaccine had already subjected participants to delayed second doses. Most participants in the British trial were given the two doses at least nine weeks apart. British regulators said on Wednesday that the first dose had 73 percent efficacy in protecting against Covid-19 in the period between that shot taking effect and a second shot being administered. But scientists cautioned that those figures held for a subset of trial participants and had a limited underlying immunological rationale.

Scientists have also expressed concerns about the Oxford-AstraZeneca group not having enough data on older people to fully assess the vaccine’s efficacy in that group. Andrew Pollard, the director of the Oxford Vaccine Group, said in an interview on Wednesday that more evidence in older people would emerge from an ongoing American trial that has nearly enrolled all 30,000 of its volunteers.

The United States and the European Union have indicated that they are unlikely to authorize the Oxford-AstraZeneca vaccine until at least February.

When given in two full-strength doses, the regimen authorized by Britain, AstraZeneca’s vaccine showed 62 percent efficacy in clinical trials — considerably lower than the roughly 95 percent efficacy achieved by Pfizer and Moderna’s shots. No one who received the vaccine in the clinical trials developed severe Covid-19 or was hospitalized.

British regulators said that the vaccine’s efficacy appeared to rise to 80 percent in a smaller group of volunteers who were given the two doses roughly three months, rather than a single month, apart, a result that has not been published but that nevertheless emboldened the regulators to authorize a longer gap between doses.

Professor Pollard said that the longer interval provoked higher levels of antibodies in participants. And that finding, he said, may help solve a puzzle that has hung over the Oxford-AstraZeneca group: why the vaccine had a 90 percent efficacy in volunteers who were given a half-strength, rather than full-strength, initial dose. Those volunteers happened to get their two doses further apart, making it likely that the higher efficacy was a result of the elongated gap between doses, and not the size of the initial dose, as originally believed.

Menelas Pangalos, the executive in charge of much of AstraZeneca’s research and development, said in an interview on Wednesday that the company would now work to refine the interval between doses, focusing on a possible “sweet spot” of 8 to 12 weeks. But scientists said that any such efforts required considerably more data.

And analysts cautioned that Britain’s health service may struggle to persuade people to take a vaccine that appears less effective than other available shots, but that nevertheless could hasten the end of the pandemic.

Much of the world is looking to AstraZeneca in part because it has set more ambitious manufacturing targets than other Western vaccine makers. It has said that it expects to make up to three billion doses next year — a haul that, at two doses per person, would be enough to inoculate nearly one in five people worldwide. The company has pledged to make the vaccine available at cost around the world until at least July 2021, and in poorer countries into perpetuity.“This is very good news for the world,” Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said of British regulators’ go-ahead. “It makes a global approach to a global pandemic much easier.”

For Prime Minister Boris Johnson of Britain, who has faced withering criticism for his handling of the pandemic, the rollout of the Oxford-AstraZeneca could bring some relief. The government on Wednesday put more than three-quarters of England in a virtual lockdown, and delayed the reopening of secondary schools in January.

Since authorizing Pfizer’s vaccine on Dec. 2, Britain has used it to vaccinate 617,000 people. But the country has struggled to administer it beyond hospitals and doctor’s offices, leaving some of its highest-priority recipients, like nursing home residents, still vulnerable.


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