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OCTAVE trial: Initial data on vaccine responses in patients with impaired immune systems

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 OCTAVE trial is one of the largest studies in the world so far into post-SARS-CoV-2 vaccination in immunocompromised patients. Supported by the NIHR Clinical Research Network as a designated urgent public health COVID-19 study, so far 2,577 participants have enrolled in the study across 20 UK sites.

The study is evaluating the immune responses following COVID-19 vaccination in patients with immune-mediated inflammatory diseases such as cancer, inflammatory arthritis, diseases of the kidney or liver, or patients who are having a stem cell transplant.

A variety of immune tests were performed on blood samples taken before and/or after COVID-19 vaccination in around 600 people recruited across the UK.

Initial findings from the study have been published as a pre-print on the Lancet pre-print site.

Initial findings

The initial data shows that 40% of people in the patient groups studied mounted a low serological immune response after two SARS-CoV-2 vaccines.

The data also shows that approximately 11% of immunocompromised patients fail to generate any antibodies 4 weeks after two vaccines. Failure to generate antibodies is found at a higher proportion in some specific patient subgroups. In particular, in patients with ANCA-Associated Vasculitis who have received Rituximab treatment.

Looking in detail at patient vaccine response within each of the disease subgroups included in the study, researchers found that a significant proportion of the participants generate lower levels of SARS-CoV-2 antibody reactivity, when compared with healthy subjects after two SARS-CoV-2 vaccines.

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 no current agreed clinical cut off to measure COVID-19 vaccination response.

Prof Iain McInnes, lead of the OCTAVE trial, and Vice Principal and Head of the College of MVLS at the University of Glasgow, said: “The roll-out of the vaccine programme was extremely important for these vulnerable groups of patients, however due to their underlying medical conditions and treatments, which can weaken their immune systems, we were concerned that people with these medical conditions may not receive optimal protection, so it was, and remains, extremely important to investigate this unanswered question.

“While 40% of these clinically at-risk patent groups were found to have a low or undetectable immune response after a double dose of the vaccine, we are encouraged that this figure isn’t higher. However, it is possible even partial protection may be clinically beneficial, and this is something we will closely monitor.”

“We would continue to encourage all people and especially those patients within these clinically at-risk groups to make sure they receive their vaccine doses if they haven’t done so already.”

Professor Nick Lemoine, Medical Director of the NIHR Clinical Research Network said: “The preliminary results from the NIHR-supported OCTAVE trial provide important evidence around the immune response generated by two of the most widely used COVID-19 vaccines amongst immunocompromised patients. While the immune response has been shown to be low from this initial data, the findings highlight the pressing need for further research to optimise vaccine delivery so we can best protect those with weakened immune systems from this disease.”

Dr Rob Buckle, Chief Scientist of the Medical Research Council, part of UKRI, which co-funded the trial, said: “Today’s results will be of concern for the subset of people within those who are immunosuppressed for whom the vaccine didn’t trigger a large protective response. We’re funding an extension to the OCTAVE study to give third jabs to this group, which we hope will deliver 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 and responsive studies like this, to inform our vaccine roll-out and government decision-making in real time.”

The data reported in the pre-print includes the post-vaccine immune response results from the first 600 participants recruited 4 weeks post second dose. As the study progresses, around 3000 people in total will be recruited.

Participants in the study have all received either COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) or ChAdOx1 Vaccine (AstraZeneca) as part of the National COVID19 vaccination programme.