Examining the Immunological Effects of COVID-19 Vaccination in Patients with Conditions Potentially Leading to Diminished Immune Response Capacity – The OCTAVE Trial

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

SARS-COV-2 vaccines have been shown to be efficacious primarily in healthy volunteer populations and population level studies. Immune responses following SARS-CoV-2 vaccination are less well characterised in potentially immune vulnerable patient groups, including those with immune-mediated inflammatory and chronic diseases (inflammatory arthritis [IA] incorporating rheumatoid arthritis [RA] and psoriatic arthritis [PsA]; ANCA-Associated Vasculitis [AAV]; inflammatory bowel disease [IBD]); hepatic disease (HepD), end stage kidney disease requiring haemodialysis (HD) without or with immunosuppression (HDIS); solid cancers (SC) and haematological malignancies (HM), and those that have undergone haemopoietic stem cell transplant (HSCT). The OCTAVE trial is a multi-centre, multi-disease, prospective cohort that will comprehensively assess SARS-CoV-2 vaccine responses within and between the abovementioned disease cohorts using common analytical platforms in patients recruited across the United Kingdom (UK). The majority of subjects received either COVID-19 mRNA Vaccine BNT162b2 (Pfizer/BioNTech) or ChAdOx1 Vaccine (AstraZeneca formerly AZD1222) as part of the UK National COVID19 vaccination programme. As of 13 th August 2021; 2,583 patients have been recruited. We report herein the humoral and T cell immune response results from the first 600 participants recruited where serology data are available at baseline, pre-second vaccine dose (boost) and/or 4 weeks post second dose. We also include in the analysis, data obtained from 231 healthy individuals from the PITCH (Protective Immunity from T cells in Healthcare workers) study. Overall, in comparison to PITCH where 100% of tested individuals (n=93) generated anti-Spike antibodies after vaccine doses, 89% of patients within OCTAVE seroconverted 4 weeks after second vaccine dose. By corollary, approximately 11% of patients across all disease cohorts fail to generate antibodies that react to SARS-CoV-2 spike 4 weeks after two vaccines. Failure to generate spike reactive antibodies was found at a higher proportion in some specific patient subgroups, particularly AAV (72.4%), HD-IS (16.7%) and HepD (16.7%). Importantly, all recruited AAV patients had received Rituximab; a targeted B cell depletion therapy. Furthermore, even in those who seroconverted, 40% of patients across disease cohorts generate lower levels of SARS-CoV-2 antibody reactivity compared to healthy subjects after two SARS-CoV-2 vaccines; the functional significance of these findings in providing protection from subsequent SARS-CoV-2 exposure is not currently known. In contrast to the observed serological response, evaluation of the Spike-specific T cell response revealed that across all patient sub-groups (including AAV) a response similar to healthy individuals was generated. Our data argue strongly for further vaccination strategies to optimise humoral immune responses against SARS-CoV-2 in patients with chronic diseases and/or patients on immune suppressive therapies. 

Author list


Pamela Kearns, University of Birmingham - NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences

Stefan Siebert, University of Glasgow

michelle willicombe, Imperial College London; Imperial College Healthcare NHS Trust

Charlotte Gaskell, University of Birmingham

Amanda Kirkham, University of Birmingham

Sarah Pirrie, University of Birmingham

Sarah Bowden, University of Birmingham

Sophia Magwaro, University of Birmingham

Ana Hughes, University of Birmingham

Zixiang Lim, University of Oxford

Stavros Dimitriadis, University of Oxford

Sam M. Murray, University of Oxford

Thomas Marjot, University of Oxford

Zay Win, University of Oxford

Sophie L. Irwin, University of Oxford

Georgina Meacham, University of Oxford

Alex G. Richter, University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Peter Kelleher, Imperial College London

Jack Satsangi, University of Oxford

Paul Miller, NHS Foundation Trust - St. Georges University Hospitals

Daniel Rea, University Hospitals Birmingham NHS Foundation Trust

Gordon Cook, University of Leeds

Lance Turtle, University of Liverpool - NIHR Health Protection Research Unit in Emerging and Zoonotic Infections

Paul Klenerman, University of Oxford - Peter Medawar Building for Pathogen Research

Susanna Dunachie, University of Oxford - Peter Medawar Building for Pathogen Research

Neil Basu, University of Glasgow - Institute of Infection, Immunity and Inflammation

Thushan I. de Silva, University of Sheffield - Department of Infection, Immunity & Cardiovascular Disease; Sheffield Teaching Hospitals NHS Foundation Trust - South Yorkshire Regional Department of Infection and Tropical Medicine

David Thomas, Imperial College London

Eleanor Barnes, Oxford University Hospitals NHS Foundation Trust

Carl S. Goodyear, University of Glasgow

Iain McInnes, University of Glasgow

Novel Coronavirus SARS-CoV-2


Preprints with The Lancet