CHEKOV: CHEcKpoint Inhibitor effects On SARS-CoV-2 Vaccination

Data on the effectiveness of prophylactic vaccination in cancer patients is limited. Patients receiving Immune Checkpoint Inhibitors (ICIs) are likely to differ from other groups due to the unique mode of action of these agents: blocking homeostatic controls that normally limit T-cell response generation and effector functions, which include direct cytotoxicity but also providing B-cell help essential for establishing effective antibody responses. It is unknown whether ICI-exposure affects the size and quality of the T-cell/antibody response to SARS-CoV-2 infection and vaccination, possibly skewing them away from virus control to enhance immune pathology, and, conversely, whether virus infection alters ICI-induced immunity including patterns associated with auto-immunity. We will describe the immune interactions between ICI treatment and immunity to SARS-CoV-2 infection and vaccination using an already established blood sample collection from well-defined cohorts including: i) healthy donors pre- and post-vaccine, ii) serial samples from people with melanoma (with linked clinical data) receiving ICIs pre- and post-vaccine, and iii) melanoma patients infected with SARS-CoV-2 while treated with ICIs. We will first measure IgG, IgA and neutralising antibody responses to spike and nucleocapsid antigens using MesoScale assays. This will provide a rapid initial assessment of vaccine efficacy in patients. We will then characterise T-cell responses to overlapping peptide pools spanning the open reading frames of the main virally encoded T-cell antigens (spike, nucleocapsid and matrix proteins) using an established intracellular cytokine assay capable of measuring six effector functions (IFN-g, TNF-a, IL-4, IL-10, IL-17, and cytotoxic degranulation by surface exposure of CD107a) on CD8+ and CD4+ T-cells.