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

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.

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.