Maternal mRNA Vaccination: Immunological Principles and Evidence Gaps in Infant Protection

Maternal messenger RNA (mRNA) vaccination can generate maternal immunity and antibodies for passive infant protection. However, clinical evidence derives predominantly from the SARS-CoV-2 vaccines BNT162b2 and mRNA-1273, limiting generalization across the platform. This narrative review examines three questions: what determines maternal immune responses, what governs placental antibody transfer, and how immunological findings relate to infant clinical protection. Studies generally support preserved immune responsiveness during pregnancy, but associations with gestational timing are difficult to separate from dose number, previous infection, and time since antigen exposure. Transfer requires interpretation of maternal and cord-blood concentrations, because high transfer ratios do not necessarily indicate high infant antibody levels. Postnatal antibody decline and variant-dependent neutralization further limit inference from measurements at delivery. Observational studies associate maternal vaccination with reduced COVID-19-associated infant hospitalization, although residual confounding and heterogeneous exposure histories complicate comparisons between schedules. No validated infant antibody threshold predicts protection against SARS-CoV-2 infection or hospitalization. Evidence for other pathogens and self-amplifying RNA remains predominantly preclinical. Maternal immunogenicity, placental transfer, and antibody persistence therefore provide complementary evidence but cannot substitute for clinical outcomes. Future products require pregnancy-specific safety assessment and prospective studies linking maternal responses, functional antibody transfer, and postnatal persistence to clinically meaningful protection throughout infancy.