Placenta-informed Precision Maternal Vaccinology: Designing Pregnancy Vaccines for Selective Antibody Transfer, Neonatal Protection, and Infant Immune Programming

Maternal immunization has increasingly been recognized as a practical strategy to protect infants during the earliest months of life, a period when the neonatal immune system remains immature and vulnerability to infection is high. Despite this progress, most vaccination programs during pregnancy have traditionally emphasized maternal antibody generation as the primary outcome. The placenta – an active biological interface that regulates antibody transfer to the fetus – has received comparatively less attention in vaccine design and evaluation. This systematic review aimed to examine current evidence on maternal vaccination through a placenta-centered perspective and to explore whether a placenta-informed framework could refine how vaccines in pregnancy are designed, evaluated, and timed to enhance neonatal protection. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 reporting guidance, a structured search was performed across PubMed/MEDLINE, PubMed Central, Embase, Scopus, Web of Science, and the Cochrane Library. Studies addressing maternal vaccination, Fc-mediated immunoglobulin G (IgG) transport, placental immunobiology, and neonatal immune outcomes were screened through sequential title–abstract and full-text assessment. Eligible studies were synthesized qualitatively. From 902 identified records, 51 studies met the inclusion criteria. Across multiple vaccine platforms – including pertussis, influenza, respiratory syncytial virus, SARS-CoV-2, and candidate Group B Streptococcus vaccines – several determinants of antibody transfer were consistently observed. IgG subclass distribution, Fc glycosylation profiles, and neonatal Fc receptor (FcRn)-mediated transport strongly influenced the efficiency and selectivity of transplacental antibody transfer. Gestational timing of vaccination, maternal inflammatory status, placental physiology, and fetal factors further modified these processes, ultimately shaping the repertoire of antibodies reaching the newborn. Maternal vaccination should be understood not only as maternal immune priming but as part of an integrated maternal–placental–fetal immunologic system. A placenta-informed precision vaccinology framework – considering vaccine platform, antibody quality, and optimal gestational timing – may improve neonatal protection and guide future maternal vaccine development.