Skip to main content

This site is best viewed with a modern browser. You appear to be using an old version of Internet Explorer.

Study reveals vaccine responses in patients with impaired immune systems

24/08/2021
This article is more than two years old.

A national study has found that a significant proportion of clinically at-risk patients with certain immunocompromised or immunosuppressed conditions, mount a low, or undetectable, immune response after two doses of the same COVID-19 vaccine. 

The ongoing multi-centre OCTAVE 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. Initial data from the study have been published on the Lancet pre-print site

The study is led by the University of Glasgow and co-ordinated by the University of Birmingham’s Cancer Research UK Clinical Trials Unit. Researchers from Oxford University Hospitals (OUH) and the University of Oxford’s Nuffield Department of Medicine are leading the research involving patients with gastrointestinal diseases.

OCTAVE, one of the largest studies in the world into post-SARS-CoV-2 vaccination in immunocompromised patients, is funded by the Medical Research Council (MRC) and also involves groups in the University of Liverpool, Imperial College London and Leeds Teaching Hospitals NHS Trust, as well as researchers in Oxford, Glasgow and Birmingham.

The study used a variety of state-of-the-art immune tests performed on blood samples taken before and/or after COVID-19 vaccination in around 600 people recruited across the UK. OCTAVE's early data show that 40% of people in the patient groups studied mounted a low serological immune response after two SARS-CoV-2 vaccines. 

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

The researchers found that a significant proportion of patients studied as part of OCTAVE 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 90% of those with Rituximab treated ANCA-associated vasculitis, 54% of those with inflammatory arthritis, 21% of those on haemodialysis, 42% of those on haemodialysis receiving immunosuppressive therapy, 51% of those  with hepatic disease, 17% of those with solid cancer, 39% of those with haematological malignancies, and 33% 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 can tell us 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 Ellie Barnes, who is leading the OCTAVE study in Oxford, said: "We are studying groups of patients whose underlying medical conditions and treatments can weaken their immune systems. It has therefore been vitally important to investigate what level of protection these people receive from the vaccines.

"It was encouraging to see that a double dose of vaccine generated an immune response in 60% of these vulnerable patients. But that still leaves 40% of these clinically at-risk patients with a low or undetectable response. It is important to say that even a relatively low level of antibodies may protect you from infection - we just do not know yet. And T cells, that were generally detected in vulnerable patients may also play an important role in protecting people from severe disease. We will continue to study how we might protect these patients, including investigating the effects of administrating an alternate vaccine dose to this group.

"These preliminary findings - and our ongoing research - will be help to inform how best to vaccinate patients with chronic conditions and protect them from COVID-19 infection in the future. We would encourage everyone - and especially those people in these clinically at-risk groups - to ensure they receive their vaccine doses if they have not done so already."

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 OCTAVE (Observational Cohort Trial-T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2) study looks at those with immune mediated inflammatory diseases including rheumatoid arthritis, psoriatic arthritis, ANCA-Associated Vasculitis, inflammatory bowel disease, as well as hepatic disease and renal failure. So far more than 2,500 patients have been recruited to the trial making it one of the largest global studies in which detailed immune response is being assessed post-SARS-CoV-2 vaccination.

The data reported in the pre-print paper includes the post-vaccine immune response results from the first 600 patients recruited four weeks after their second dose of either the Pfizer/BioNTech or Oxford-AstraZeneca vaccines.

Image credit: Hakan Nural via Unsplash