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Fourth Covid vaccine dose offers higher immunity than third jab booster, Cambridge study shows



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A fourth Covid vaccine dose can offer higher immunity than the third jab booster, according to new research.

The results from the COV-BOOST trial, run at NIHR Cambridge Clinical Research Facility (CRF) at Cambridge University Hospitals NHS Foundation Trust (CUH) show that a fourth dose mRNA vaccine is safe and boosts antibody levels higher than that of a third dose.

A Covid-19 vaccine
A Covid-19 vaccine

Fourth doses are currently offered in the UK to the most vulnerable - those aged 75 or over, people living in care homes for older people, and anyone aged 12 or more who is immunosuppressed.

This has been a precautionary strategy to maintain high levels of immunity prior to the COV-BOOST study data being available. A wider group of people may be offered a fourth dose booster later this year.

Researchers published their findings on Tuesday in The Lancet Infectious Diseases.

Professor Saul Faust, trial lead and director of the NIHR Southampton Clinical Research Facility, said: “These results underline the benefits of the most vulnerable people receiving current spring boosters and gives confidence for any prospective autumn booster programme in the UK, if the Joint Committee on Vaccination and Immunisation considers it needed at that time.”

A new study on fourth doses of a Covid vaccine has been published
A new study on fourth doses of a Covid vaccine has been published

The COV-BOOST study, led by University Hospital Southampton, provided the world’s first data on the safety, immune responses and side-effects of a third Covid-19 vaccine dose in mix-and-match schedules. The study was key to shaping the UK’s autumn booster programme and provides evidence for global vaccination efforts.

The latest findings show that fourth dose mRNA booster vaccines are well tolerated in people who received Pfizer as a third dose. They are also effective at increasing both antibody and cellular immunity up to and above baseline and peak levels observed following third dose boosters.

In the fourth dose study across 10 UK sites, 166 people who had received a third dose of Pfizer, following Pfizer or AstraZeneca initial doses in June 2021, were randomised to receive full dose Pfizer or half-dose Moderna as a fourth dose, around seven months after their third dose.

Professor Krishna Chatterjee, director of the NIHR Clinical Research Facility in Cambridge, who is leading the trial at CUH, said: “Our CRF teams continue to work tirelessly to find vaccines and treatments to protect against Covid-19 and the results of the COV-BOOST study are testament to this.

A Covid-19 vaccination is administered
A Covid-19 vaccination is administered

“We couldn’t do it without the 230 local people who volunteered to take part in all phases of this trial either, and we thank them, along with all who are involved in ongoing research to tackle the virus as the pandemic evolves.”

While pain at vaccination site and fatigue were the most common side effects, there were no vaccine-related serious adverse events and fourth doses were safe and well tolerated.

Current COV-BOOST sub-studies are investigating the interval between second and third doses, fourth doses of mRNA vaccines, an Omicron variant vaccine and fractional dosing in people aged between 18 and 30 years old.


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