Persistence of memory: lifespan dynamics of the human antiviral antibody reactome

The human antiviral antibody reactome provides a cumulative molecular record of immune exposures. Using high-resolution VirScan profiling, we compared epitope-level antibody responses across early childhood and adulthood. Infants are born with maternal IgG antibodies, but these antibodies decay rapidly and are replaced by endogenous responses to ~22 new viral exposures within three years. Pediatric antibody reactivities remain highly dynamic until about age 7 and are broad in epitope specificity but largely short-lived. In contrast, adult reactomes are remarkably stable and individualized, enabling accurate longitudinal donor identification (Immunoprint, > 99.99% accuracy). Stability varies by viral family, with Pneumoviridae and Picornaviridae persisting more robustly than Coronaviridae or Orthomyxoviridae. Across ages, immunodominant epitopes and initial binding strength predict response persistence. Longitudinal profiling highlights biological and epidemiological drivers of reactome change. This population-level, age-stratified atlas informs our understanding of immune memory and development with applications to vaccine design, surveillance, and precision public health.