The coronavirus pandemic shows that, in extremis, vaccinology conventions can be challenged © Carlos Osorio/Reuters

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The writer is a science commentator

In 2016, as a yellow fever outbreak crept closer to major cities in Angola and the Democratic Republic of Congo, the World Health Organization took a calculated gamble.

Faced with vaccine shortages, it recommended the splitting of doses. More than 7m children and adults in Kinshasa, among others, received only a fifth of the usual dose. That fractional amount, researchers later found, induced good levels of protective antibodies that were still detectable a year later. A year of protection is better than none in a raging epidemic.

Could veering off-script in the rollout of Covid-19 vaccines also be in the public interest? The Pfizer/BioNTech vaccine, the first to be deployed in the US and UK, officially requires two doses given 21 days apart. But, instead of issuing first doses and reserving supplies to give boosters later, some people advocate dispensing all doses now and giving boosters when further supplies allow. In the US, this option means 40m would get a first dose of the Pfizer/BioNTech vaccine, instead of 20m receiving two doses. The UK is currently rolling out 800,000 doses, with another 4m due by the end of December.

The idea was floated recently by Scott Gottlieb, the former head of the US Food and Drug Administration who now sits on the board of Pfizer. “I feel very strongly that we should get as many shots in arms as possible, right away,” Mr Gottlieb told USA Today last week. “The reality is that one dose is partially protective. I just fundamentally disagree with [saving half the supply for January].” The vaccine is 52 per cent effective after the first dose, rising to 95 per cent after the booster.

His view is that immediate deployment maximises the health benefits of a life-saving intervention. It is not a risk-free strategy: unforeseen delays to supplies next year could hamper the rollout of boosters. Still, leaving vulnerable people unvaccinated while second doses languish for weeks in fridges, is also a risk.

There is another point in Mr Gottlieb’s favour: there is no firm evidence that boosters must be timed precisely to be efficacious. While second doses dramatically enhance protection, dosing intervals are not set by any immutable commandments of vaccinology. The WHO vaccine tracker, for example, shows a variety of dosing schedules, mostly modelled on past convention.

“It’s like a random number generator,” says Danny Altmann, professor of immunology at Imperial College London. “Some doses are 28 days apart, while others are 21 or 14. That doesn’t reflect the fundamentals of the immune system but a tweaking of the trials that gave slightly better data. You could probably merge them all and come out with one common protocol that would work pretty well for all of them.” A handful of trials have offered a second or third dose on day 56. 

Intriguingly, in the Oxford/AstraZeneca vaccine trial, some volunteers in the under-55 subgroup showing the highest efficacy had their second jabs as long as eight weeks after the first. Routine boosters for other diseases are also put off for multiple reasons — holidays, clinic closures, delayed deliveries, forgetfulness — without efficacy being a worry.

As Professor Altmann concludes: “If I were an NHS adviser or a vaccine producer running a huge logistical operation, I’d probably want to stick to protocol. But if you ask me: does the timing of the booster really, really matter all that much? Probably not. In vaccinology, when push comes to shove, if we’re trying to save lives we sometimes break protocol, as happened with yellow fever.”

The coronavirus pandemic also shows that, in extremis, vaccinology conventions can be challenged. The dosing error that dogged the Oxford/AstraZeneca trial was unexpectedly associated with better results. Scientists have not ruled out mixing and matching first and second doses from different vaccines, depending on availability.

Volunteers who drop out of clinical trials after a first dose of one Covid-19 vaccine in order to receive a different, approved jab, will be a fascinating cohort to watch.

There might be just enough scientific leeway, and encroaching danger, to reasonably discuss bending the rules to deploy all Covid-19 vaccine doses now. Christmas approaches. Infection rates are rising. Hospitals are filling up. More vaccines are coming next year. Mr Gottlieb’s approach of emptying the armoury now is a gamble — but so is holding back half of the ammunition when other cavalries are on their way. 

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