Optimising Vaccine Efficacy in Multi-Disease Patient Cohorts with SARS-CoV-2 vaccine failure (OCTAVE-DUO)

The multi-centre OCTAVE study is a flagship UK CTIMP evaluating the immune response following COVID-19 vaccination in people with immune mediated inflammatory diseases, hepatic/gastrointestinal disease, renal failure, solid or blood cancers, solid organ transplant, and patients who have received haematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cells (CAR-T). Uniquely, OCTAVE seeks to comprehensively assess SARS-COV-2 vaccine responses within and between disease cohorts using common platforms in patients recruited across the UK. Early data show that approximately 30% of patients mount a low, or undetectable immune response after two homologous SARS-CoV-2 vaccines evaluated by serology based assays. It is not known whether re-vaccination booster strategies will initiate, or further enhance the immune response to thereby provide appropriate protection from COVID-19 in these prevalent and clinically vulnerable disease cohorts. Leveraging our existing and successful OCTAVE consortium, and its related infrastructure, the OCTAVE-DUO study will investigate the effectiveness of homologous and heterologous re-vaccination strategies using licensed vaccines to generate a protective immune response in patients within our disease cohorts who have sub-optimal primary vaccine responses. Patient will be stratified based on low/no serological vaccine response and state-of-the-art optimised immune assays will characterise the magnitude, functionality, and durability of T cell and humoral immune responses following re-vaccination. NHS data linkage and standard pharmacovigilance approaches will determine the level of protection afforded by revaccination and adverse events related to a third vaccine exposure. Identifying immune and clinical parameters that predict which patient populations will benefit from re-vaccination strategies will critically inform UK health and government policies during the ongoing pandemic.