NEW YORK (NYTIMES) - As governments around the world rush to vaccinate their citizens against the surging coronavirus, scientists are locked in a heated debate over a surprising question: Is it wisest to hold back the second doses everyone will need, or to give as many people as possible an inoculation now - and push back the second doses until later?
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 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 (Jan 1). "We're going to keep doing what we're doing."
But on Sunday, Dr Moncef Slaoui, scientific adviser of Operation Warp Speed, the federal effort to accelerate vaccine development and distribution, offered up 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 gotten 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 Ms Natalie Dean, a biostatistician at the University of Florida.
The vaccines authorised so far in the United States 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.
After the body has had time to study up on 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's 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 rollout began last month in the United States, second shots of the vaccines have been held back to guarantee that they will be available on schedule for people who have already gotten their first injections.
But in Britain, doctors have been told to postpone appointments for second doses that had been scheduled for January, so that those doses can be given instead as first shots to other patients. Officials are now pushing the second doses of both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines as far back as 12 weeks after the first one.
In a regulatory document, British health officials said that AstraZeneca's vaccine was 73 per cent effective in clinical trial participants three weeks after the first dose was given and before the second dose was administered. (In cases in which participants never received a second dose, the interval ended 12 weeks after the first dose was given.)
But some researchers fear the delayed-dose approach could prove disastrous, particularly in the United States, where vaccine rollouts 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."
Federal health officials said last week that some 14 million doses of the Pfizer-BioNTech and Moderna vaccines had been shipped out across the country. But as of Saturday morning, just 4.2 million people in the United States had gotten their first shots.
That number is most likely an underestimate because of lags in reporting. Still, the figure falls far short of the goal that federal health officials set as recently as last month to give 20 million people their first shots by the end of 2020.
Many of these rollout woes are caused by logistical issues - against the backdrop of a strained healthcare system and skepticism around vaccines. Freeing up more doses for first injections won't solve problems like those, some researchers argue.
Associate Professor 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 that they got, and we don't know what a mix and match might do."
In an emailed statement, Dr Peter Marks, director of the Centre for Biologics Evaluation and Research at the Food and Drug Administration, endorsed only the strictly scheduled two-dose regimens that were tested in clinical trials of the vaccines.
The "depth or duration of protection after a single dose of vaccine," he said, cannot be determined from the research published so far. "Though it is quite a reasonable question to study a single-dose regimen in future clinical trials, we simply don't currently have these data."
There is no dispute that second doses should be administered sometime near the first dose.
"They key is to expose the immune system at a time when it still recognises" the immunity-stimulating ingredients in the vaccine, said Dr Angela Rasmussen, a virus expert affiliated with Georgetown University.
During a public health emergency, "companies will tend to pick the shortest period they can that gives them that full, protective response," said Ms Dean of the University of Florida.
But it's unclear when that critical window really starts to close in the body. Prof Akiko Iwasaki, an immunologist at Yale University who supports delaying second doses, said she thought the body's memory of the first injection could last at least a few months.
Doses of other routine vaccines, she noted, are scheduled several months apart or even longer, to great success. "Let's vaccinate as many people as possible now, and give them the booster dose when they become available," she said.
Dr Robert Wachter, an infectious disease physician at the University of California, San Francisco, said he was originally skeptical of the idea of delaying second doses.
But the disappointingly slow vaccine rollout in the United States, coupled with concerns about a new and fast-spreading variant of the coronavirus, have changed his mind, and he now believes this is a strategy worth exploring.
"The past couple weeks have been sobering," he said.
Other researchers are less eager to take the gamble. Delaying doses without strong supporting data "is like going into the Wild West," said Dr Phyllis Tien, an infectious disease physician at the University of California, San Francisco.
"I think we need to follow what the evidence says: two shots 21 days apart for Pfizer, or 28 days apart for Moderna."
Some experts also fear that delaying an immunity-boosting second dose might give the coronavirus more opportunity to multiply and mutate in partly protected people.