Single-Cell Multi-Omics Reveals Dynamic Chromatin Remodeling of Adaptive Immunity During Prime-Boost Vaccination

Vaccination induces durable adaptive immunity, yet how transcriptional and chromatin programs are dynamically established and reorganized across successive vaccine doses remains poorly understood. Here, we performed paired single-nucleus RNA sequencing and chromatin accessibility profiling of peripheral blood mononuclear cells collected from four individuals at ten time points spanning primary and booster immunization with the inactivated SARS-CoV-2 vaccine BBIBP-CorV. More differentially expressed genes and accessible regions were detected after primary than booster vaccination. Notably, independent public Hi-C data provided structural context for candidate DAR-gene associations. In B cells, AP-1 motif accessibility decreased dynamically after primary vaccination, followed by increased plasma cell differentiation and secretory programs. In T cells, signature scores decreased on day 1 after primary vaccination and were accompanied by remodeling of transcription factor-associated chromatin accessibility. These intracellular changes were accompanied by temporal reorganization of T and B cell communication and the emergence of distinct multicellular modules associated with primary and booster responses. Together, our findings describe temporal changes in gene expression and chromatin accessibility across circulating T and B cells following primary and booster vaccination in this cohort.