Oxford patients to test third COVID-19 vaccine for people with weakened immune systems

A new clinical trial to determine whether a third dose of vaccine will improve the immune response for people who have weakened immune systems has launched in Oxford.

The LCRN-supported OCTAVE DUO study will offer people who are immunosuppressed or immunocompromised a Pfizer, Moderna or Novavax vaccine to determine whether this will give a stronger immune response than two doses.

This will include 190 patients at Oxford’s John Radcliffe and Churchill hospitals with inflammatory bowel disease on immunosuppressant medication; with end-stage chronic liver disease, liver transplants or on immunosuppressant medication and lymphoma patients.

The £2.2 million study will build on the OCTAVE trial. Preliminary data published in The Lancet shows 89% of people who are immunocompromised or immunosuppressed generate antibodies following vaccination, and 60% generated a strong antibody response following two doses of a vaccine.

However, 40% of people in these groups mounted a low, or undetectable, immune response after two doses and the level of antibody response varies between the groups studied.

The level of antibodies required for protection from COVID-19 is still not known, and it is likely that T cells also play an important role in protecting people from the virus. These findings therefore don’t provide a conclusive assessment of the protection vaccines offer people with weakened immune systems.

Up to 1,200 patients who are already involved in the OCTAVE study or those with other at-risk conditions involved in parallel studies will be recruited to the OCTAVE DUO trial.

The study, co-funded by the government’s Vaccines Taskforce and UK Research and Innovation (UKRI) and led by the University of Glasgow and University of Birmingham, will analyse in detail the immune response of this group to the vaccine and the durability of this protection. It will also use healthcare records to determine whether any participants are later diagnosed with COVID-19.

Initial results are expected later this year to inform the UK’s COVID-19 vaccine deployment in these specific at-risk groups. The trial will follow the patients to mid-2022 and offer more detailed information at that stage about the immune responses that develop in these groups. 

The government is carefully considering the findings of the OCTAVE trial and will also consider any further appropriate advice – including from the independent Joint Committee on Vaccination and Immunisation (JCVI) - for those who are immunosuppressed as part of regular reviews of the latest data and evidence on vaccine efficacy and effectiveness.

Professor Ellie Barnes, leading the study in Oxford, said: “Our work on the OCTAVE study has revealed that 30% of our participating patients in Oxford – and 40% nationally - mount a relatively low immune response to the COVID vaccination. This is of concern, as it means a significant number of vulnerable people may not be protected.

“We need to do more investigations to determine what level of antibody response provides protection against severe COVID. The level of antibodies required for protection from COVID-19 is still not known, and it is likely that T cells also play an important role in protecting people from severe disease.

“These findings don’t yet provide a conclusive assessment of the protection vaccines offer people with weakened immune systems but measuring the immune response to a third booster vaccine that we can now offer to participants is the right thing to do next.”

Read more about the study on the NIHR website