Trial shows lower immune response to COVID vaccines for some at-risk patients

Initial data from the ongoing, NIHR-supported OCTAVE trial show that a significant proportion of clinically at-risk patients with specific immunocompromised or immunosuppressed conditions mount a low or undetectable immune response after two doses of the same COVID-19 vaccine.

The initial findings, published in Preprints with The Lancet, show that approximately 11% of immunocompromised patients fail to generate any antibodies four weeks after two vaccines. Failure to generate antibodies is found at a higher proportion in some specific patient subgroups, such as those with ANCA-Associated Vasculitis who have received Rituximab treatment.

The proportion of patients with lower levels of antibody reactivity was dependant on the disease cohort, with 87% of those with Rituximab treated ANCA-Associated Vasculitis, 51% of those with inflammatory arthritis, 29% of those on Haemodialysis, 42% of those on Haemodialysis receiving immunosuppressive therapy, 36% of those with Hepatic disease, 10% of those with solid cancer, 33% of those with Haematological malignancies, and 17% of patients who have undergone haemopoietic stem cell transplant responding less well than the baseline for healthy subjects.

However, the significance of these findings in terms of what they reveal about vaccine protection from exposure to COVID-19 is not currently known, as there is currently no agreed clinical cut off to measure COVID-19 vaccination response.

The OCTAVE trial is one of the largest studies in the world investigating COVID-19 vaccination in immunocompromised patients. Supported by the NIHR as a designated urgent public health study, so far more than 2,500 participants have enrolled across the UK, including participants at University Hospital Southampton in Wessex.

The initial results of the OCTAVE trial were followed by the launch of a new government-funded trial investigating a third dose of COVID-19 vaccine for people with weakened immune systems.

The trial, known as OCTAVE DUO, will offer people who are immunosuppressed or immunocompromised an additional dose of a Pfizer, Moderna or Novavax COVID-19 vaccine to determine whether this will give a stronger immune response than two doses.

Recruitment to OCTAVE DUO has started in Wessex, with eligible participants from the OCTAVE trial and those with other at-risk conditions involved in parallel studies, invited to take part.

The OCTAVE DUO 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 to vaccines and the durability of this protection. It will also use healthcare records to determine whether any participants are later diagnosed with COVID-19.

Professor Iain McInnes, Head of the College of Medical, Veterinary and Life Sciences at the University of Glasgow who leads the OCTAVE and OCTAVE DUO studies, said:

“It is hugely important for us to urgently understand the effectiveness of COVID-19 vaccines in people who have immune-mediated inflammatory diseases, cancer, and diseases of the kidney or liver.

“Our first study to answer this question is the OCTAVE study which has shown that there is a group of patients who may not mount a sufficient immune response.

“We are pleased to now roll-out of the OCTAVE DUO trial, to investigate the effects of a third dose on this particular group of patients who have shown an undetectable or low vaccine response. We hope to provide answers to this very important unanswered question.”

Professor Pam Kearns, Director of the University of Birmingham’s Cancer Research UK Clinical Trials Unit which is co-ordinating both OCTAVE and OCTAVE DUO, said:

“The pandemic has been particularly concerning for millions of people in the UK who have conditions or long term illnesses which place them at greater risk of severe illness and death from COVID-19.

“Together with our preliminary findings from OCTAVE, this new study will be instrumental in helping inform how best to vaccinate patients with chronic conditions, and protect them from COVID-19 infection in the future.”

Dr Rob Buckle, Chief Scientist of the Medical Research Council, part of UKRI, which co-funded the trial, said:

“While most of us are relieved to be vaccinated to protect ourselves and those around us, today’s results investigating the outcome for people with immunosuppression will be of concern to the subset for whom the vaccine didn’t trigger a large protective response.

“This new study of giving third jabs to this group is critical research which we hope will demonstrate a much-needed immunity boost or identify those who could benefit from other interventions.

“One of the real strengths of the UK’s scientific response to the pandemic has been the way that we’ve assembled teams of experts to lead cutting-edge studies like this, to inform our vaccine roll-out and government decision-making in real time.”