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Here, we provide a concise overview of recent developments in the identification of immunogenic epitopes in human apolipoprotein B-100 for immunization against atherosclerotic cardiovascular disease. Major steps forward toward a clinical application of vaccines include the design of humanized mouse models, tetramer-based identification of antigen-specific T cells, and novel analysis tools, such as single-cell RNA sequencing and cytometry by time of flight, to assess temporal and spatial changes in immune cells in atherosclerotic cardiovascular disease.