Booster shots of the Oxford/AstraZeneca covid-19 vaccine work well, but as yet there is no evidence that we will actually need them, according to new data from the team who developed it.
The Oxford University researchers gave a third dose of vaccine to 90 double-jabbed volunteers aged between 18 and 55 who had received their second dose on average 30 weeks earlier. The shot raised antibody levels above where they were 4 weeks after the second dose and also boosted T-cells. These form a central part of our immune system, hunting down and killing host cells infected with the virus.
“It is very encouraging, if we were to need it,” says of the University of Oxford. However, at this point there is no evidence of vaccine-induced immunity waning enough to warrant a booster campaign. Even after a single dose, says Lamb, antibody levels remain high for at least a year and T-cell responses are “relatively strong” at 6 months. “[Immunity] does decay but it’s still there… it’s not falling off a cliff,” she says. Immunity would be expected to persist even more strongly after two doses, she says, but that data is not yet available. Immune memory should provide long-term protection.
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“At the moment we don’t know whether boosters are needed,” says , also at Oxford. “It is something where we need to keep looking at the data and make decisions as the months go by about whether that protection we have is lost.” The study is about preparedness, not policy, he says.
The vaccine used in the study was the original, but the team is also testing a booster vaccine tweaked to be more effective against the beta variant, which is showing some signs of escaping vaccine-induced immunity. That trial started last week. The delta variant does not seem to be evading the vaccines and tweaking to deal with it is low on the list of priorities, says Pollard.
Data from the first trial has shown no signs that the third dose produces a harmful immune response to the benign virus used to deliver the active ingredient. Lambe has previously flagged that up as a potential cause of booster failure.
The results – which are published in a non-peer-reviewed – only apply to the AstraZeneca vaccine. Pfizer/BioNTech and Moderna are testing , and an ongoing clinical trial in the UK is testing these and five others – AstraZeneca, Janssen, Novavax , Valneva and CureVax.
Even if third shots work, they remain controversial when many countries have barely started administering first ones. “At this point with high levels of protection in the UK population and no evidence of that being lost, to give third doses now while other countries have zero doses is not acceptable,” says Pollard.
Nonetheless, he says, “we do have to be in a position where we could boost if it turned out that was necessary.”
A separate arm of the same experiment found that a second dose of the AstraZeneca vaccine produces a powerful immune boost even after a very long delay of up to of 45 weeks. Most countries recommend a gap of no more than 12 weeks between first and second doses. The result is mainly of relevance to countries where vaccine supply is limited and second doses may not be available on the recommended time frame, says Lambe.
The result is in keeping with what we know about the immune response to vaccines, says Pollard, but should not be interpreted as a reason to deliberately extend the gap beyond 12 weeks, as that risks leaving people partially protected for longer. “There’s always a trade off,” says Pollard. “We don’t really know at this moment with one dose how long you can safely sit there with good levels of protection.”
Countries with irregular vaccine supplies were given another boost from a different experiment called , which is looking at the effectiveness of mixing and matching different vaccines across the two doses. It found that mixing the AstraZeneca and Pfizer vaccines, in either order, produced stronger immune responses than giving the same one twice.
“This argues for flexibility where local circumstances require it,” says chief investigator Matthew Snape of the University of Oxford. “You can’t always guarantee supplies. You may get a big delivery of one type of vaccine and then another delivery some months later of another type of vaccine and you’re actually obliged to then combine them into different schedules.” We need to know which mixtures to avoid, he says.
The results are also a boost to people who have had adverse reactions to a first dose of one vaccine, and may also be of relevance to the booster debate as they suggest that mixing and matching the third dose may produce a stronger response too.
There are many caveats, however. The results are from a 4-week dose regime; data from a 12-week gap is still being crunched. Some of the immune response is also still under investigation and the study does not include the protection offered against variants of concern such as delta.
“The study is reassuring that using a mixed vaccine approach is not only safe but can potentially give immune responses that are as good or better than those induced by single vaccine regimens,” says Peter Openshaw of Imperial College London.
However, we should resist the temptation to see it as evidence for routinely mixing and matching. There is not yet enough data to make the call, says Snape.
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