Investigating the Impact of Tumor Necrosis Factor Inhibitors on SARS-CoV-2 mRNA Vaccine-induced Immunity in Immunocompromised Patients with Immune-mediated Inflammatory Diseases

Immunocompromised patients are at increased risk of viral infections and adverse outcomes following infection, including intensive care unit admission and in-hospital mortality. Further, they run the risk of shedding virus for longer, leading to increased risk of transmission or the generation of immune escape variants. While vaccination reduces the risk of infection in immunocompromised patients, it may be less effective in patients treated with immunomodulatory or immunosuppressive therapies. In this study, we will focus on immunocompromised adult patients with inflammatory bowel disease (IBD). Patients with IBD are often treated with drugs that block an inflammatory molecule called tumor necrosis factor (TNF). Treatment with TNF blocking agents is known to impair antibody responses to vaccines developed for seasonal influenza and SARS-CoV-2. In this proposal, we will conduct an in-depth investigation of the immune cells (T and B cells) in these treated IBD patients to further understand the detailed mechanism driving the defect in antibody responses to SARS-CoV-2 mRNA vaccination and how we can counteract the defect. Our studies will fill a critical gap in understanding how immunosuppressive treatments, such as TNF blockers, affect the immune response of immunocompromised patients to SARS-CoV-2 vaccination, with broader implications to other viral vaccines. Importantly, we hope to inform public policy on the optimal vaccine development and regimens for the immunocompromised.