Timing of maternal Tdap vaccination: A dynamic balance between antibody induction and placental transfer efficiency

Abstract

Background: Tetanus, diphtheria, acellular pertussis (Tdap) vaccination in pregnancy protects newborns against pertussis, but the influence of gestational age (GA) at vaccination on maternal and neonatal immune profiles remains incompletely understood. This study aimed to characterize the effect of GA at Tdap vaccination on several antibody features during pregnancy and at birth, and to assess transplacental antibody transfer. Methods: 96 pregnant women received Tdap at different GAs between week 16 and 32 within a Belgian, prospective non-randomized controlled trial. Maternal blood was collected pre-vaccination, at multiple timepoints post-vaccination, and at delivery, alongside cord blood at birth. Tdap-specific total IgG and IgG subclasses were evaluated alongside Fc-mediated effector functions. Multivariate analyses were applied to define composite immune patterns. Results: Post-vaccination, robust immune responses were observed across cohorts. At delivery, maternal total IgG and IgG1 against PRN, DT, and TT were higher with later vaccination, whereas other subclasses and functional responses were largely comparable. Cord blood profiles partially paralleled maternal patterns without reaching significance, and no significant effect of vaccination-to-delivery interval was detected. IgG transfer ratios generally declined with advancing GA; functional antibody transfer was largely unaffected. Multivariate analyses highlighted higher maternal antibody response profiles at delivery with later vaccination, while cord blood profiles were generally unaffected. Conclusion: Maternal Tdap antibody response profiles at delivery are influenced by vaccination timing, while neonatal antibody profiles at birth appear largely comparable within the limits of the study. These findings support current recommendations for Tdap administration between 16 and 32 weeks of gestation and underscore the flexibility of this window for routine antenatal care.