Fc Glycan-Mediated Regulation of Placental Antibody Transfer.
Despite the worldwide success of vaccination, newborns remain vulnerable to infections. While neonatal vaccination has been hampered by maternal antibody-mediated dampening of immune responses, enhanced regulatory and tolerogenic mechanisms, and immune system immaturity, maternal pre-natal immunization aims to boost neonatal immunity via antibody transfer to the fetus. However, emerging data suggest that antibodies are not transferred equally across the placenta. To understand this, we used systems serology to define Fc features associated with antibody transfer. The Fc-profile of neonatal and maternal antibodies differed, skewed toward natural killer (NK) cell-activating antibodies. This selective transfer was linked to digalactosylated Fc-glycans that selectively bind FcRn and FCGR3A, resulting in transfer of antibodies able to efficiently leverage innate immune cells present at birth. Given emerging data that vaccination may direct antibody glycosylation, our study provides insights for the development of next-generation maternal vaccines designed to elicit antibodies that will most effectively aid neonates.
['Jennewein|Madeleine F|MF|', 'Goldfarb|Ilona|I|', 'Dolatshahi|Sepideh|S|', 'Cosgrove|Cormac|C|', 'Noelette|Francesca J|FJ|', 'Krykbaeva|Marina|M|', 'Das|Jishnu|J|', 'Sarkar|Aniruddh|A|', 'Gorman|Matthew J|MJ|', 'Fischinger|Stephanie|S|', 'Boudreau|Carolyn M|CM|', 'Brown|Joelle|J|', 'Cooperrider|Jennifer H|JH|', 'Aneja|Jasneet|J|', 'Suscovich|Todd J|TJ|', 'Graham|Barney S|BS|', 'Lauer|Georg M|GM|', 'Goetghebuer|Tessa|T|', 'Marchant|Arnaud|A|', 'Lauffenburger|Douglas|D|', 'Kim|Arthur Y|AY|', 'Riley|Laura E|LE|', 'Alter|Galit|G|']
D000293:Adolescent D000328:Adult D001530:Belgium D015550:Cell Degranulation D015331:Cohort Studies D005260:Female D006031:Glycosylation D015395:Histocompatibility Antigens Class I D006801:Humans D007074:Immunoglobulin G D007231:Infant, Newborn D007694:Killer Cells, Natural D008213:Lymphocyte Activation D008297:Male D010920:Placenta D011134:Polysaccharides D011247:Pregnancy D011961:Receptors, Fc D017452:Receptors, IgG D000074084:THP-1 Cells D014481:United States D014611:Vaccination D055815:Young Adult
antibody glycosylation maternal vaccination ADCC antibody functionality neonatal immunology trans-placental transfer