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Fourth COVID-19 Vaccine Boosts Antibody Levels Higher Than Third Dose

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COVID-19 vaccines given as fourth doses in the UK offer excellent boosting immunity protection, according to the latest results from a nationwide NIHR-supported study.


The latest results  from the COV-BOOST trial, ran at the Oxford University Hospitals NHS Foundation Trust show that a fourth dose mRNA vaccine is safe and boosts antibody levels - higher than that of a third dose.


Researchers have published their findings today in The Lancet Infectious Diseases.


Fourth doses of COVID-19 vaccines have been offered as a spring booster for those most vulnerable in the UK. This has been a precautionary strategy to maintain high levels of immunity prior to the study data being available. A wider group of people may be offered a fourth dose booster later this year.


The latest findings show that fourth dose mRNA booster vaccines for COVID-19 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.


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


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. These were approximately seven months after their third dose.


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.


The two vaccines trialled in the fourth dose sub-study were those deployed in the UK NHS third dose booster campaign:

  • Pfizer (Pfizer-BioNTech)
  • Moderna (half dose – 50 micrograms)


“We knew that it was important to offer a fourth dose to those most vulnerable earlier in the year. These new study findings support that decision and provides the public with the confidence that fourth doses are both safe and even more effective than 3rd doses at boosting immunity against COVID-19.


"It is thanks to the endless efforts and contribution of study participants and staff across the UK that we can keep discovering more about the use of vaccines, and they continue to play a pivotal role just as they have done throughout the pandemic."


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 young people aged 18-30 years.


Reference: Munro APS, Feng S, Janani L, et al. Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial. Lancet Infect. Dis. doi: 10.1016/S1473-3099(22)00271-7.


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