(197) Multi-omic Signatures of Vaccine Responses in Healthy Early Adolescents

Introduction/Rationale: Early adolescence represents a distinct phase of immune maturation between childhood and adulthood, yet this age window has rarely been profiled in depth at a systems level. This study examines how vaccine-induced immune responses are shaped during this critical developmental window.

Methods: We followed 11–13-year-olds for up to two years with repeated PBMC collection, including visits before and after combination (Tdap/MCV4/HPV/influenza), stand-alone influenza, and COVID-19 (prime/booster) vaccination. We generated scRNA-seq, Olink plasma proteomics, flow cytometry, influenza-specific IgG, and HAI titers. These readouts were analyzed across adolescent vaccine exposures, and influenza responses were compared to young and older adult influenza vaccine cohorts.

Results: Adolescents mounted distinct humoral and transcriptional responses to influenza vaccination versus adults. At the humoral level, adolescents displayed an age-associated pattern of strain-specific influenza IgG and HAI titers, with less cross-reactive memory IgG than adults. At the transcriptional level, adolescents showed strong activation of naïve T cells, NK cells, and monocytes, whereas adults had greater vaccine-responsive changes in the B cell compartment. Across four adolescent visits, we observed naïve T cell activation with minor variation in magnitude and distribution of responding cell types. We searched for non-naïve, clonally expanded cells within phenotypically naïve T cells and found no TCR clonotype expansion across vaccination visits, suggesting that activation signaling in this population is not primarily driven by TCR-specific responses.

Conclusion: Early adolescent immune responses demonstrate non-specific transcriptional activation across lineages and across vaccine visits - highlighting early adolescence as a unique period of immunity with distinct vaccine-mediated responses compared to adults.