Single-cell transcriptomics reveals pediatric immune responses to COVID-19 vaccination.

Inactivated vaccines are critical to COVID-19 immunization, yet the cellular and molecular mechanisms driving pediatric responses warrant detailed characterization. We use single-cell transcriptomics to delineate the immune landscape of peripheral blood mononuclear cells in children vaccinated with CoronaVac. We uncovered a two-phase program: the primary dose establishes a memory foundation via expansion of survival-programmed memory B cells and a shift in CD8+ T cells toward stress adaptation. The booster triggers an effector response marked by plasma cell differentiation, class-switching, and a pan-B cell type I interferon signature. Concurrently, vaccination reprograms monocytes into a pro-inflammatory, antigen-presenting state enriched for interferon-stimulated genes. This activation is counterbalanced by expanded myeloid-derived suppressor cells and FOXP3 + regulatory T cells, which employ PGE2 signaling to restrain excessive cytotoxicity and orchestrate helper T cell differentiation. Together, our atlas demonstrates that pediatric immunity to inactivated vaccines is tightly orchestrated, balancing antiviral programs with regulatory mechanisms to ensure safe protection.