Abstract
As the UK and US embark on large-scale coronavirus vaccine booster campaigns, Graham Lawton considers the evidence on whether you should get another shot
OVER the next few months, about 30 million fully vaccinated people in the UK will be invited to have a third dose of a covid-19 vaccine. The surprise decision to run such a large booster campaign – everyone over 50 is included – was made off the back of multiple lines of evidence, none of them definitive. So what is the rationale behind it? And if you are offered a booster, should you take it?
The UK isn't the only country looking to roll out third doses for a large portion of the population. Last week, the US Centers for Disease Control and Prevention endorsed the use of booster shots for people aged 65 and over, and for those with underlying health conditions or in jobs with a high risk of exposure to the virus.
The UK government's decision was based on advice from the Joint Committee on Vaccination and Immunisation (JCVI), which says the move is “precautionary”. The JCVI itself was largely guided by an ongoing clinical trial called COV-Boost, based at the University Hospital Southampton NHS Foundation Trust, UK.
In June, COV-Boost recruited 2833 people aged 30 and over who were already double vaccinated with either the Pfizer/BioNTech or Oxford/AstraZeneca vaccines. They all received a third dose of one of seven covid-19 vaccines – Pfizer/BioNTech, Oxford/AstraZeneca, Moderna, Novavax, Valneva, Janssen and Curevac – or a control, a vaccine against meningitis. Half of the recruits were over 70 and a “decent number” of those were over 80, says chief investigator Saul Faust. Half had received Pfizer/BioNTech for their first two doses and half Oxford/AstraZeneca.
Over the next four weeks, the volunteers kept a record of any side effects and on day 28 came in for a blood test to measure their antibody levels, T-cell responses and also a “killing assay” to see how potent their blood was at neutralising the virus.
According to Faust, some of the vaccines produced “several-fold” increases in antibody levels and also improved T-cell responses, suggesting that they significantly strengthen protection against the virus. The vaccines were well tolerated in the small number of people in the trial.
The full results from the trial are expected in October, but the JCVI evidently saw enough in the interim results to give the green light to a booster campaign. Its booster of choice is the Pfizer/BioNTech vaccine, to be given at least six months after a person's second shot. A half dose of the Moderna vaccine – which like Pfizer/BioNTech is an mRNA vaccine – can also be used. People who can't take an mRNA vaccine because of adverse reactions can have the Oxford/AstraZeneca vaccine as a booster.
The decision to go ahead was widely welcomed by scientists and medics. Neil Ferguson at Imperial College London said on Twitter that the booster campaign should help the UK avoid another lockdown this winter.
The decision doesn't mean boosters will become an annual event. “Our advice does not imply there will be future booster programmes,” says Anthony Harnden, deputy chair of the JCVI.
We can be confident that the boosters are acceptably safe, says Faust. “I know they [the JCVI] will be taking the side effects into account when they make their recommendations.” However, the trial didn't include enough people to pick up rare adverse events such as the blood-clotting disorders occasionally seen with the Oxford/ AstraZeneca vaccine.
The JCVI also considered data from Public Health England showing that vaccine-induced protection starts to fade 10 weeks after the second dose. After 20 weeks, protection against symptomatic disease falls from about 90 per cent to 70 per cent with Pfizer/BioNTech and from 65 per cent to 50 per cent with Oxford/AstraZeneca. Protection against hospitalisation also wanes slightly. The decline becomes more pronounced with age.
Booster campaigns are also supported by data from Israel, which started the world's first booster campaign in August amid a surge of infections among double-vaccinated people. “They were on an extremely bad trajectory,” says Sarah Walker, chief investigator of the UK's COVID-19 Infection Survey. “There is no doubt that after they introduced boosters, their hospitalisation rate dropped.”
Concerns have also been raised that existing vaccines don't adequately protect against the delta variant, which is now the dominant strain in the UK, and that boosters may have to be modified to deal with it or other “variants of concern”. These fears are unjustified, says Sharon Peacock, executive director of the COVID 19 Genomics UK Consortium. “The vaccines are really effective against the variants of concern that are circulating,” she says.
That also heads off another worry around boosters, the immunological phenomenon called original antigenic sin. This is when a modified vaccine reawakens an old immune response rather than provoking a new one, and it could render booster shots designed to target future variants ineffective. So it is good news that, for the time being, current vaccines are doing pretty well against newer variants.
Concerns have been raised in the past as well about multiple dosing of the Oxford/AstraZeneca vaccine, because repeated exposure to the virus vector used to deliver the active ingredient could elicit a harmful immune response. Results so far suggest that this isn't a problem with a third dose, says Faust.
There is also no evidence that having booster vaccinations can somehow “overload” the immune system or produce a diminishing response over time. “That's not a credible concern. It won't overload the immune system,” says Sarah Gilbert at the University of Oxford, who co-developed the Oxford/AstraZeneca vaccine.
All of this points squarely in one direction. “If you get called up for your booster vaccine, get it,” says Roger Kirby, president of the UK's Royal Society of Medicine.
The booster campaign isn't just about individual protection, says David Oliver, a consultant physician at the Royal Berkshire Hospital, UK, but also about safeguarding public health and preventing hospitals from being overwhelmed this winter.
Some people, however, have chosen to decline their third dose because of issues around vaccine equity. covid-vaccinations So far, only 2.2 per cent of people in low-income countries have received at least one dose.
Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, has called for a moratorium on booster shots until the end of the year, to enable every country to vaccinate 40 per cent of its population. But this requires political will from wealthy nations – if you decline your shot, it won't be sent to a country that needs it more.