Fc Glycan-Mediated Regulation of Placental Antibody Transfer
Name
nihms-1531669.pdf
Description
Accepted version
Size
3.21 MB
Format
Adobe PDF
Checksum (MD5)
ba160180f47389e292d8558232734ab5
Author(s)
Jennewein, Madeleine F
Goldfarb, Ilona
Dolatshahi, Sepideh
Cosgrove, Cormac
Noelette, Francesca J
Krykbaeva, Marina
Das, Jishnu
Sarkar, Aniruddh
Gorman, Matthew J
Fischinger, Stephanie
Date Issued
2019
Journal
Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2019 Elsevier Inc. 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. Antibodies with a specific glycan modification and with the ability to activate NK cells are selectively transferred across the placenta to the neonate.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Center for Gynepathology Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2019.05.044
