Third-dose boosters offer long-term protection from COVID-19, study run in Exeter finds

Third dose COVID-19 booster vaccines offer lasting protection after several months, according to the latest results of a nationwide trial.

The NIHR-supported COV-BOOST study, run across England and Wales at sites including Royal Devon and Exeter Hospital, part of Royal Devon University Healthcare NHS Foundation Trust (RDUH), has provided data to underpin the UK’s booster programmes since 2021.

New analysis, published online in the Journal of Infection, provides data on immune responses eight months after third doses of several COVID-19 vaccines.

The insight could be important around the globe if longer-term protection becomes a higher priority when choosing vaccines for booster programmes.

Researchers leading the study at the University Hospital Southampton found adenovirus-based vaccines (such as Janssen or Oxford-AstraZeneca) may lead to similar immune responses as mRNA vaccines (such as Moderna or Pfizer-BioNTech) at around seven months after the third dose of vaccine. They also report that lower doses of mRNA vaccines may offer lasting protection as boosters.

Booster study

In December 2021, COV-BOOST provided the world’s first data on the safety and immunogenicity of a third dose in mix and match schedules.

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.

Last year, the study reported strong immune responses 84 days after third jabs in several approved COVID-19 vaccines.

A fourth dose sub-study also found that an mRNA vaccine is safe and boosts antibody levels - even higher than that of a third dose.

The NIHR Clinical Research Network South West Peninsula (CRN SWP) supported the efforts of the Royal Devon research team to recruit more than 200 volunteers to participate in the COV-BOOST study in and around Exeter.

Professor Michael Gibbons, NIHR CRN SWP Clinical Director and Consultant Respiratory Physician at RDUH, said:

“These latest results from COV-BOOST provide important new information about the long-term protection offered by vaccine boosters, that will help inform the way they are used worldwide. It is another success for the teams delivering the study both nationally and locally, who have already given us vital evidence that shaped booster policy at the height of the pandemic.

"As always, our heartfelt thanks go to all those in the South West and beyond who volunteered to take part in this research.”

Longer-lasting immunity

Third and fourth doses of COVID-19 vaccines have been offered to people considered vulnerable or at higher risk in the UK.

Professor Saul Faust, trial lead and Director of the NIHR Southampton Clinical Research Facility, said:

“The rapid development and delivery of COVID-19 vaccines has been vital to forging a path out of the pandemic. Looking to the future, vaccines that provide longer-lasting immunity may now be preferred to those that need to be given at shorter intervals. Different doses may be an option depending on the duration of immune response.

“This further data, taken over 240 days after third doses, will support global policymaking on the choice of future boosters and inform manufacturing.”

Professor Andy Ustianowski, National Clinical Lead for the UK NIHR Covid Vaccine Research Programme and Chair of COV-BOOST Data Safety Monitoring Board, said:

"The fact that we are able to live with the Covid-19 virus is thanks to innovative vaccine research happening here in the UK and further afield. COV-BOOST, which is funded and delivered by the NIHR and others, has helped us gain an even better understanding into the effectiveness of third- and fourth-dose vaccinations, which offer vital protection to those most vulnerable to infection.

 "While life in the UK has largely returned to normal, Covid-19 has not gone away and insight into the long-term protection offered by different vaccines could help policymakers around the world when developing their booster programmes."

UK-wide research effort

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)

The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites.

The latest report analyses the responses to third doses of the original (wild type) vaccines from 817 participants in seven study arms.

The current mRNA vaccines recommended by the Joint Committee on Vaccination and Immunisation (JCVI) are bivalent vaccines that have been upgraded to target two circulating variants of COVID-19. This study used wild-type mRNA vaccines that targeted the original strain of COVID-19 and therefore cannot be directly compared to the vaccines used in more recent campaigns.

COV-BOOST is 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 former Vaccine Taskforce (now the COVID Vaccine Unit in the UK Health Security Agency) 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.