Summary: A new study identifies how vaccine-triggered antibodies from pregnant women cross the placenta to reach their newborns. The findings clarify which antibody features the placenta favors and offer guidance for designing maternal vaccines that better protect infants.
Source: Mass General
Background
Vaccination is one of the most effective public health tools for preventing infectious disease, yet newborns remain especially vulnerable. Their immune systems are immature at birth, and direct vaccination in the first days of life is often ineffective. To protect infants during this critical window, mothers transfer antibodies across the placenta before birth. Until now, the precise rules that govern how the placenta selects and delivers maternal antibodies to the fetus were not well understood.
Key findings
Researchers at the Ragon Institute of MGH, MIT and Harvard, working with collaborators in obstetrics and gynecology, used an approach called systems serology to compare antibody profiles in maternal blood and matching umbilical cord blood. The study focused on vaccine-induced antibodies to pertussis (whooping cough) and extended the analysis to antibodies targeting influenza and respiratory syncytial virus (RSV).
The team found that the placenta does not transfer all antibodies equally. Instead, it preferentially transfers antibodies that are particularly effective at activating natural killer (NK) cells—important innate immune cells that are abundant and functional in the first days of life. These NK-activating antibodies carry specific molecular features on their Fc domains: notably digalactosylated Fc glycans. Those glycan structures increase antibody binding to the neonatal Fc receptor (FcRn) and to FCGR3A, a receptor that engages NK cells.
Implications for newborn protection and vaccine design
These findings explain why some maternal antibodies—such as those produced after measles vaccination or infection—are effectively passed to babies, while antibodies for other pathogens may be delivered less efficiently. By showing that the placenta favors antibodies with particular Fc glycan patterns and NK-activating potential, the study identifies testable targets for improving maternal immunization strategies.
If vaccines can be formulated or scheduled to induce antibodies with the glycosylation patterns the placenta prefers, maternal vaccination could offer stronger, more reliable protection to infants immediately after birth. This approach would leverage the innate immune capabilities newborns already possess—especially NK cells—rather than relying solely on the infant’s developing adaptive immune system.
Study details and authors
The research combines clinical sampling of mothers and umbilical cord blood with advanced systems serology profiling of antibody quantity, Fc receptor binding, glycosylation state, and functional activity. Co-senior authors Galit Alter, PhD, of the Ragon Institute and Massachusetts General Hospital, and Laura Riley, MD, formerly of MGH and now at Weill Cornell Medicine, led the effort. The lead author is Madeleine Jennewein of the Ragon Institute.
Highlights
- NK cell-activating antibodies are selectively transferred across the placenta.
- Digalactosylated Fc glycans are preferentially transferred to the fetus.
- Digalactosylated antibodies show enhanced binding to FcRn and FCGR3A.
- Although neonatal adaptive immune responses are immature, neonatal NK cells respond robustly to immune complexes.
Summary of the research
Newborn vulnerability to infectious disease persists despite the global success of vaccination because neonatal immune responses are limited and can be blunted by maternal antibodies in some contexts. Maternal prenatal immunization aims to protect infants by delivering maternal antibodies before birth. Using systems serology, the authors characterized Fc-dependent features that differ between maternal and neonatal antibody pools. The neonatal antibody profile is skewed toward NK cell-activating functions and specific Fc glycan structures that favor placental transport and engagement of innate immune cells present at birth. As vaccination has been shown to influence antibody glycosylation, these results point to actionable pathways for designing next-generation maternal vaccines that more reliably produce antibodies the placenta will transfer to protect newborns.
Funding and acknowledgements
Support for the study included grants from the National Institutes of Health and institutional awards supporting the investigators. The authors note that continued work will explore optimal timing and vaccine formulations to maximize protective maternal-to-infant antibody transfer.
About this research article
Original research: “Fc Glycan-Mediated Regulation of Placental Antibody Transfer” by Laura Riley et al., published in Cell. The study advances understanding of placental selection of maternal antibodies and guides development of improved maternal vaccination strategies.