Vaccine Responses in Early Age.

Neonates and infants exhibit fundamentally distinct immune responses compared to adults, resulting in increased susceptibility to infectious diseases and reduced vaccine efficacy. These age-specific responses are characterized by developmental constraints affecting both adaptive and innate immunity. T cell-independent (TI) responses to polysaccharide vaccines are severely impaired due to reduced transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) expression on neonatal B cells, while T cell-dependent (TD) responses are compromised by Th2 bias in the CD4+ T cell compartment, and by restricted T follicular helper (Tfh) cell development. Emerging data suggest that cytokines such as IL-6 have completely opposite effects on Tfh cell development between adults and neonates. Germinal center (GC) B cell responses are further constrained by delayed follicular dendritic cell (FDC) maturation, impaired B cell receptor (BCR) signaling, and elevated frequencies of IL-10-producing regulatory B cells. The overall immunosuppressive phenotype associated with early age extends to the neonatal innate immune system as exhibited by altered dendritic cell (DC) subset distribution, decreased IL-12p70 production, lower expression of MHC class II and co-stimulatory molecules, and increased IL-10 secretion. To overcome these immune constraints, various adjuvants that are shown to enhance immune response to vaccines in adults are considered for early age vaccines. Although some of these adjuvants show promising results in animal experiments, mechanistic studies need to be conducted in detail since adult and neonatal in vivo environments may dictate different outcomes between the two age groups, especially because early-life adjuvant exposure may have long-lasting effects on immune system programming. Elucidation of age-specific immune responses to vaccines and adjuvants will help develop age-tailored strategies to develop safe and effective pediatric vaccines.