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Fourth Covid jab can give higher immunity than initial booster, study finds | Vaccines and immunisation



A fourth dose of a Covid vaccine can ramp up the body’s immune defences beyond the peak achieved after a third dose, research suggests.

A second booster – often a fourth dose of a Covid vaccine – is currently offered in the UK to those aged 75 or over, people living in care homes for older people, and those over the age of 12 who are immunosuppressed.

Now researchers say they have found a fourth dose can rescue immune responses that have waned since a third jab.


“We’ve demonstrated a fourth dose of Covid-19 vaccines can produce a substantial boost to both the antibody and cellular immunity when you give them more than six months after the third dose,” said Prof Saul Faust, who led the trial and is director of the NIHR Southampton clinical research facility.

Writing in the Lancet Infectious Diseases, researchers involved in the UK-based Cov-Boost trial report how they measured immune responses in 166 participants who received a fourth Covid jab on average seven months after having had a Pfizer/BioNTech jab as their third dose. All participants had initially had either two doses of the Pfizer/BioNTech jab or two doses of the Oxford/AstraZeneca vaccine.

Half were randomly allocated to receive a full dose of the Pfizer/BioNTech Covid jab as their fourth vaccination, while the others were given half a dose of the Moderna jab. No serious adverse events were linked to the vaccines.

The team analysed data from 133 participants, finding that 14 days after receiving the fourth jab, there was a 1.6-fold increase in antibodies among those who received the Pfizer/BioNTech vaccine, and a more than twofold increase among those who received the half-dose Moderna jab, compared with 28 days after the third dose, when antibody levels were still at their peak.


Increases were seen for those over and below 70 years of age.

In addition, levels of antibodies and T-cells increased substantially between the day before the fourth vaccination and 14 days after for both types of fourth jab.

“Our results for immunogenicity are also consistent with the little observational evidence on vaccine effectiveness available from Israel, which indicates increased protection against symptomatic infection and severe illness from a fourth-dose booster,” the team write.

Faust added that those who had little waning of their immune responses before their fourth dose gained only a limited increase in their immune responses as a result of the booster – with similar findings for others who had a recent history of a Covid infection. “That indicates there may be a ceiling, a maximum antibody level with the T-cell response effects,” he said.


Faust said it was up to the UK’s Joint Committee on Vaccination and Immunisation to decide whether a second booster should be offered more widely.

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Some experts have suggested in the current circumstances those yet to reach middle age might never be offered another Covid jab.

But Prof Danny Altmann, an immunologist at Imperial College London, said Omicron still posed a serious threat, adding that the new study demonstrated the added value of a fourth dose.

“Just because our first-generation vaccines wane rapidly and offer rather permeable protection nowadays, does not suggest we should give up and have no further boosters,” he said.

“On the contrary, [given] many of us, even with high apparent antibody levels, actually show [very little] protective neutralisation of Omicron, there is all the more urgency to use [fourth] doses – in all age groups – to boost levels back up into the protective range.”


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