Respiratory syncytial virus hospitalizes hundreds of thousands of infants annually, yet newborns lack the immune maturity to mount robust defenses. Maternal RSV vaccination has changed that calculus — but precisely how protective antibodies travel from mother to infant, and how durable that protection is, involves molecular machinery that researchers are only now mapping in detail.
This review synthesizes current mechanistic understanding of maternally transferred RSV immunity across three interlocking levels. First, the neonatal Fc receptor (FcRn) actively selects and transports IgG across the placenta, with IgG1-dominant, prefusion-F-specific antibodies — the predominant product of modern RSV vaccines such as Abrysvo — showing particularly efficient transfer. Second, IgG subclass composition matters not only for transfer efficiency but for serum half-life once in neonatal circulation, influencing how long passive immunity persists. Third, and perhaps most intriguingly, the glycosylation state of IgG Fc regions appears to modulate engagement with Fcγ receptors, potentially shaping effector functions beyond simple viral neutralization — including antibody-dependent cellular cytotoxicity and phagocytosis. Systems serology data suggest these Fc-dependent functions may be qualitatively enriched in neonatal blood relative to maternal blood, hinting at selective placental transfer of functionally superior antibody variants.
The broader significance lies in what this mechanistic picture implies for vaccine optimization. Vaccination timing during pregnancy critically determines transplacental antibody concentrations; too early may allow antibody titers to wane before delivery, while confounding factors such as preterm birth or placental pathology can sharply reduce transfer efficiency. The glycosylation angle is particularly underexplored — modifications that alter sialylation or fucosylation patterns could substantially amplify or diminish neonatal protection, a lever that next-generation maternal vaccine platforms might deliberately target. The evidence base remains heterogeneous and largely observational, but this synthesis meaningfully advances the framework for designing trials that measure not just antibody quantity but functional antibody quality in neonates.