Variability of Vaccine Responsiveness in Young Children

Abstract

Abstract Background Variability in vaccine responsiveness among young children is poorly understood. Methods Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples were collected at age 1 year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal vaccine responder (NVR), and high vaccine responder (HVR), to test for vaccine antigen–induced immune memory and for antigen-presenting cell (APC) function. Results Significantly lower specific cytokine/chemokine levels as biosignatures, measurable in nasopharyngeal secretions at infant age 1–3 weeks, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year, LVRs had fewer CD4+ T-helper 1 and T-helper 2 memory cells responsive to specific vaccine antigens. APC responses observed among LVRs, both at rest and in response to Toll-like receptor 7/8 stimulation by R848, were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs. Conclusions Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure is associated with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children.