The latest results from a UK-wide study, led by University Hospital Southampton, have demonstrated prolonged immune responses following third doses of several COVID-19 vaccines.

COV-BOOST provided the world’s first data on the safety and immunogenicity of a third dose in mix and match schedules, underpinning the UK’s autumn 2021 booster roll-out.

It compared immune response to seven vaccines 28 days after use as a third dose in people who had received two initial doses of either the AstraZeneca or Pfizer vaccines.

The latest findings, published online in the Journal of Infection, reveal strong immune responses are still seen 84 days after third jabs with five of the COVID-19 vaccines currently approved for use in the UK (AstraZeneca, Pfizer, Moderna, Janssen and Novavax vaccines). Of these vaccines, only three (Pfizer, Moderna and AstraZeneca) have been used in the UK booster programme.

Of the 2,883 people taking part aged 30 – 94 years, 2,422 had no SARS-CoV-2 infection through to their day 84 visit. In those who had two initial doses of AstraZeneca, the Pfizer and Moderna mRNA vaccines given as a third dose gave the highest anti-spike antibodies at day 84.

However, in people who had two initial doses of Pfizer there was no significant difference at day 84 between those given a third jab of AstraZeneca or Pfizer. Those given Janssen’s jab as a third dose after two doses of Pfizer showed an even stronger anti-spike antibody response at day 84.

Responses to a half (15 μg) or full (30 μg) dose of Pfizer were similar in both those who had AstraZeneca or Pfizer initial doses.

Critically, the rate that immune cell responses declined after third doses was similar between all the vaccine combinations and doses.

Saul Faust, trial lead and Director of the NIHR Southampton Clinical Research Facility, is a Professor of Paediatric Immunology and Infectious Diseases at the University of Southampton.

He said: “What COV-BOOST has shown is that most of the currently approved vaccines drive persistent protection when used as a third dose. That gives countries worldwide confidence in the value of booster programmes - and flexibility in delivering them.

“Although very high antibody levels may be useful to control a new variant spreading in society in the first few weeks after a booster jab, the longer-term protection against hospitalisation and death is perhaps the most important factor for future booster programmes.

“We also found that a half dose of the Pfizer vaccine gives similar responses as a full dose at three months, which could help in planning global vaccine supply and delivery.”

The seven vaccines trialled in the main COV-BOOST trial were:

AstraZeneca (Oxford-AstraZeneca)
Pfizer (Pfizer-BioNTech)
Moderna
Novavax
Valneva
Janssen
CureVac (first-generation vaccine no longer in clinical development)

COV-BOOST is being led by University Hospital Southampton NHS Foundation Trust and delivered by a network of trial sites across the UK. The study is funded by the Vaccine Taskforce and the National Institute for Health and Care Research (NIHR). Delivery partners are Oxford Vaccine Group (University of Oxford), Imperial College London Clinical Trials Unit, PHARMExcel Ltd and the NIHR Clinical Research Network.

Current sub-studies are investigating the interval between second and third doses, fourth doses of mRNA vaccines, an omicron variant vaccine and fractional dosing in young people aged 18-30 years (the young adult trial is funded by CEPI, the Coalition for Epidemic Preparedness Innovations Foundation).

UK COVID-19 vaccine booster study reports well-maintained immunity three months after first dose