NEW YORK • As governments around the world rush to vaccinate their citizens against the surging coronavirus, scientists are locked in a heated debate over a question: Is it wisest to hold back the second dose everyone will need, and instead give as many people as possible an inoculation now?
Since even the first shot appears to provide some protection against Covid-19, some experts believe that the shortest route to containing the virus is to disseminate the initial injections as widely as possible now.
Officials in Britain have already elected to delay the second doses of vaccines made by the pharmaceutical companies AstraZeneca and Pfizer as a way of more widely distributing the partial protection afforded by a single shot.
Health officials in the United States have been adamantly opposed to the idea.
"I would not be in favour of that," Dr Anthony Fauci, the nation's top infectious disease expert, told CNN on Friday. "We're going to keep doing what we're doing."
But on Sunday, Dr Moncef Slaoui, scientific adviser of Operation Warp Speed, the US federal effort to accelerate vaccine development and distribution, offered an intriguing alternative: giving some Americans two half doses of the Moderna vaccine, a way to possibly milk more immunity from the nation's limited vaccine supply.
The rising debate reflects nationwide frustration that so few Americans have got the first doses - far below the number the Trump administration had hoped would be inoculated by the end of 2020.
But the controversy itself carries risks in a country where health measures have been politicised and many remain hesitant to take the vaccine.
"Even the appearance of tinkering has negatives, in terms of people having trust in the process," said Dr Natalie Dean, a biostatistician at the University of Florida.
The vaccines authorised so far in the US are produced by Pfizer/BioNTech and Moderna. Britain has greenlit the Pfizer/BioNTech and Oxford/AstraZeneca vaccines.
All of them are intended to be delivered in multiple doses on a strict schedule, relying on a tiered protection strategy. The first injection teaches the immune system to recognise a new pathogen by showing it a harmless version of some of the virus' most salient features.
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GIVE A HALF DOSE
The Oxford/AstraZeneca vaccine has been plagued by uncertainty about its most effective dosage ever since data published in November showed a half dose followed by a full dose had a 90 per cent success rate, while two full shots were 62 per cent effective.
Meanwhile, the US government is considering giving some people half the dose of Moderna's Covid-19 vaccine in order to speed up vaccinations.
Data from Moderna's clinical trials demonstrated that people aged between 18 and 55 who received two 50-microgram doses showed an "identical immune response" to the standard of two 100-microgram doses, said Dr Moncef Slaoui, head of Operation Warp Speed, the US federal vaccine programme.
DELAY SECOND DOSE
Britain said last Wednesday that it would prioritise making sure that more people receive their first dose of a Covid-19 vaccine from AstraZeneca/Oxford or Pfizer/BioNTech quickly, rather than giving a second shot to those who have already had one.
The British regulator said a gap of three months between shots could boost its efficacy.
But Pfizer noted that there is no data to show that protection after the first dose is sustained after 21 days, its recommended interval before a second dose.
AstraZeneca said an interval of between four and 12 weeks was "shown in clinical trials to be safe and effective at preventing symptomatic Covid-19".
MIX AND MATCH
Britain said people could be given a mix-and-match of two Covid-19 shots on extremely rare occasions, even though there is a lack of evidence about the extent of immunity offered by mixing doses.
After the body has had time to "study" this material, as it were, a second shot presents these features again, helping immune cells commit the lesson to memory. These subsequent doses are intended to increase the potency and durability of immunity.
Clinical trials run by Pfizer/BioNTech and Moderna showed the vaccines were highly effective at preventing cases of Covid-19 when delivered in two doses separated by three or four weeks.
Some protection appears to kick in after the first shot of vaccine, although it is unclear how quickly it might wane. Still, some experts now argue that spreading vaccines more thinly across a population by concentrating on first doses might save more lives than making sure half as many individuals receive both doses on schedule.
That would be a remarkable departure from the original plan. Since the vaccine roll-out began last month in the US, second shots of the vaccines have been held back to guarantee that they will be available on schedule for people who have already got their first injections.
But in Britain, doctors have been told to postpone appointments for second doses that had been scheduled for this month, so that those doses can be given instead as first shots to other patients.
But some researchers fear the delayed-dose approach could prove disastrous, particularly in the US, where vaccine roll-outs are already stymied by logistical hurdles and a patchwork approach to prioritising who gets the first jabs.
"We have an issue with distribution, not the number of doses," said Dr Saad Omer, a vaccine expert at Yale University. "Doubling the number of doses doesn't double your capacity to give doses."
Dr Shweta Bansal, a mathematical biologist at Georgetown University, and others also raised concerns about the social and psychological effects of delaying second doses.
"The longer the duration between doses, the more likely people are to forget to come back," she said. "Or people may not remember which vaccine they got, and we don't know what a mix and match might do."