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

Abstract

Abstract 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.