1. Fc Glycan-Mediated Regulation of Placental Antibody Transfer.
- Author
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Jennewein MF, Goldfarb I, Dolatshahi S, Cosgrove C, Noelette FJ, Krykbaeva M, Das J, Sarkar A, Gorman MJ, Fischinger S, Boudreau CM, Brown J, Cooperrider JH, Aneja J, Suscovich TJ, Graham BS, Lauer GM, Goetghebuer T, Marchant A, Lauffenburger D, Kim AY, Riley LE, and Alter G
- Subjects
- Adolescent, Adult, Belgium, Cell Degranulation, Cohort Studies, Female, Glycosylation, Humans, Infant, Newborn, Killer Cells, Natural immunology, Lymphocyte Activation immunology, Male, Pregnancy, Receptors, IgG metabolism, THP-1 Cells, United States, Vaccination, Young Adult, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class I metabolism, Immunoglobulin G metabolism, Placenta metabolism, Polysaccharides metabolism, Receptors, Fc immunology, Receptors, Fc metabolism
- Abstract
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., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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