Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination

In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post-licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination.