UK launches extensive trial of third booster shots of Covid vaccines

The UK is laying the scientific foundations for giving third booster shots of Covid-19 vaccines in the autumn, with a wide-ranging clinical trial that will assess the effects of seven different jabs on people who have already received two Oxford/AstraZeneca or BioNTech/Pfizer doses.

The new Cov-Boost study will “provide data on immunogenicity and side-effects to inform the government’s decision on whether people should be revaccinated later this year and, if so, which vaccines to use in what doses for different age groups”, said Saul Faust of Southampton university, the trial’s chief investigator.

Researchers at 18 trial sites across the UK aim to recruit 2,900 volunteers who were fully immunised earlier this year. They will receive a third dose of one of the seven vaccines expected to be available in the autumn.

Some participants will receive the same AstraZeneca or Pfizer shot as their original two. Others will get a different Covid vaccine at half or full dose or the meningitis vaccine that is being used as a control. Products from Moderna, Johnson & Johnson, Valneva, CureVac and Novavax will be included, as well as AstraZeneca and Pfizer.

Matthew Snape of Oxford university, another leader of the £19.3m trial, said: “We are leading the world with Cov-Boost.” While several manufacturers are studying the effect of a third dose of their own vaccine, no one else is planning a “mix and match” study on the same scale.

The Cov-Boost researchers will study two main aspects of the volunteers’ response to a third dose. One is “immunogenicity”: the jabs’ success in boosting antibodies and T-cells that protect against Covid.

The other is adverse reactions. Another pioneering UK trial, called Com-Cov, led by Snape, reported last week that mixing first and second doses of Covid-19 vaccines increased the risk of unpleasant, short-term side-effects such as fatigue and fever.

Cov-Boost is testing the ability of booster shots of vaccines made from the original Wuhan strain of Sars-Cov-2 to protect against variants causing concern, such as those first identified in Kent, South Africa, Brazil and most recently India.

Although some manufacturers are adapting their vaccines to recognise such variants, Snape said these would not necessarily give better results than booster shots of the original jabs, because of an immunological concept called “original antigenic sin” — or, as he put it, “you never forget your first love”.

Sometimes the immune system’s memory of its response to the first shot impairs its response to a slightly changed version of the vaccine, Snape said: “It may be better to stick with the original strain but build up antibodies to a level high enough to tackle new variants.”

An important aim of the trial is “to find out whether half doses will be enough to give an adequate immune response in booster vaccines”, Faust said. “If we can use half doses, we can vaccinate twice as many people with the same amount of vaccine.”