Variability of Vaccine Responsiveness in Young Children.

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 collected at age one year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal (NVR) and high (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 old, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year old, 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 TLR7/8 stimulation by R848 were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs. CONCLUSION: Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure associates with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children.