Neonatal infections remain a leading cause of morbidity and mortality worldwide, reflecting the distinctive immunological state of early life, which prioritizes tolerance and regulatory/T helper 2 (Th2)-skewed responses over robust effector immunity. Protection during this vulnerable period relies largely on maternal immunity conveyed across the placenta and through breast milk. Transplacental IgG transport is mediated primarily by the neonatal Fc receptor (FcRn) and may be influenced by placental Fc gamma (Fcγ) receptors, IgG subclass distribution and Fc features, including glycosylation. Maternal, placental and fetal factors collectively determine the efficiency and functional quality of this transfer. Maternal vaccination increases the pool of pathogen-specific IgG available for fetal transfer, protecting mothers and conferring passive immunity to infants during the first months of life. Beyond neutralization, transferred antibodies can mediate Fc-dependent effector functions that support early protection. Maternal immunity also includes cellular components, such as maternal microchimerism and the transfer of immune cells and mediators via breast milk, which may shape neonatal immune development and vaccine responsiveness. Despite its benefits, maternal immunization may transiently dampen infant vaccine responses through mechanisms including antigen masking and inhibitory Fc-mediated signalling (the blunting effect). Current evidence indicates that these transient effects are outweighed by the protection achieved in early infancy. Future priorities include defining the long-term immunological imprint of maternal immunity, optimizing maternal vaccination timing to maximize IgG transfer, and refining infant immunization schedules to minimize interference while maintaining protection. Finally, expanding maternal immunization globally is a scalable strategy to reduce the burden of early-life infections. • Maternal immunization protects infants during the early-life immunity gap. • FcRn mediates placental IgG transport; FcγRs may modulate selectivity. • IgG transfer varies with maternal, placental and fetal factors. • Microchimerism and breast milk cells may shape neonatal immune maturation. • Maternal antibodies can transiently blunt infant vaccine immunogenicity.
Sulla et al. (Sat,) studied this question.