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

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The current vaccination strategy to provide immunological protection to SARs-Cov-2 is based on findings in healthy cohorts. The ability to generate a protective immune response after vaccination can, however, be influenced by many factors including underlying disease, and the treatment people are receiving for their disease. Our current multi-centre study (OCTAVE) is evaluating how well COVID-19 vaccination works in people with (i) immune mediated inflammatory diseases, (ii) hepatic/gastrointestinal disease, (iii) renal failure, (iv) solid or blood cancers, (v) solid organ transplant, and (vi) patients who have received haematopoietic stem cell transplant (HSCT) or chimeric antigen receptor T cells (CAR-T) or antibody deficiency.We have found that approximately 30% of these people mount either a low or undetectable immune response after undergoing standard vaccination regimes. The question now is whether giving extra vaccine doses to this vulnerable population can drive a sufficient immune response to provide the essential protection they need from SARs-CoV-2 infection. To address this, we will study our existing OCTAVE cohort and will ask whether giving an extra dose of the original or an alternative vaccine as a "boost" can drive a protective response in those who did not make a protective response to two doses. The rationale for an additional dose is supported by evidence for enhanced immunogenicity of vaccination following natural infection (a natural 3rd dose) and also the successful use of this strategy with other vaccines e.g. hepatitis B in haemodialysis patients. In parallel with an extra vaccination dose, we will take blood samples and conduct an in-depth study to see if any features of the immune response can predict which patients will benefit from re-vaccination. A range of state-of-the-art assays that have already been validated in the OCTAVE study will be used. In summary, this study will generate critical information that will inform UK health and government vaccination policies during the ongoing pandemic. It will also explore the science behind vaccination immunogenicity in at risk groups that will inform vaccination policy going forward.