AstraZeneca vaccine more effective the longer you wait for second shot, study shows

AstraZeneca’s two-dose vaccine appears to grow more effective the longer the gap between doses, lending support to Australia’s decision to recommend a three-month wait between jabs.

The data comes from a new study, published on Saturday in the Lancet and led by the scientists who developed the vaccine, that found if the second dose was given less than six weeks after the first, vaccine efficacy at preventing symptomatic infections was 54.9 per cent.

If given at least 12 weeks apart, efficacy rose to 82.4 per cent.

Some of the first vials of the locally produced AstraZeneca vaccine.

That suggests British Prime Minister Boris Johnson’s gamble, widening the interval between the two doses to increase the number of people with early protection, will pay off.

It also opens the way for other nations with out-of-control epidemics to delay the second dose, allowing them to roll out the first dose more widely.

However, the data – sourced from thousands of people enrolled in clinical trials across Britain, Brazil and South Africa – is still quite uncertain. The trial was not originally designed to test the effect of a bigger gap between doses; that was caused by delays in manufacturing.

That means the scientists could not properly randomly assign trial participants, meaning other factors could be at play that explain the results.

“Increasing the interval gives you better protection. But if you look at the range of protection in the study, it is hard to say that is an absolutely significant difference,” said University of Sydney professor of medical microbiology James Triccas.

“The most important point, and this is more relevant for other countries compared to us – there does not seem to be a negative effect of increasing that interval.”

The Therapeutic Goods Administration approved AstraZeneca’s two-dose vaccine last week. Australia has ordered 53.8 million doses.

The TGA allows nurses and doctors to administer the second dose between four and 12 weeks after the first, but the federal government’s Australian Technical Advisory Group on Immunisation recommends it is given 12 weeks apart.

A single dose of the vaccine was 76 per cent effective at preventing symptomatic COVID-19 from 22 days after administration, suggesting people enjoy strong protection while they await their second dose. It remains unclear how long that protection lasts.

The data showing that longer delays strengthen the efficacy of the vaccine is backed up by antibody data showing people who waited longer for their second jab had more than twice as many antibodies.

It is not yet clear why the efficacy would increase the longer you wait for the second dose.

AstraZeneca’s vaccine uses a modified chimpanzee virus to deliver the key vaccine ingredient to human cells. It may be because people’s immune system develops resistance to the chimpanzee virus itself – which wanes if the second dose is given with a delay.

“That’s one theory,” said Professor Triccas. “It could just be it is a property of the immune system.”

The study explains one of the central mysteries about AstraZeneca’s vaccine.

In an early study, a small group of people accidentally given lower doses of the vaccine appeared to have much better protection.

The Lancet study suggests it was not the dose, but the timing that mattered. Most people in the low-dose group received their second dose 12 weeks or more after the first.

The study was not designed to measure what effect the vaccine might have on stopping the virus spreading. But there were some tantalising clues.

Every volunteer in the trial was swabbed for COVID-19 every week, regardless of whether they had symptoms. While the vaccine does not seem to cut the number of people with asymptomatic virus, it did cut the number of people testing positive overall by 67 per cent.

Examine newsletter

Science and health explained and analysed with a rigorous focus on the evidence. Examine is a weekly newsletter by science reporter Liam Mannix. Sign up to receive it every Tuesday.