Fc glycan-mediated regulation of placental antibody transfer

Citation:

Madeleine F. Jennewein, Ilona Goldfarb, Sepideh Dolatshahi, Cormac Cosgrove, Francesca J. Noelette, Marina Krykbaeva, Jishnu Das, Aniruddh Sarkar, Matthew J. Gorman, Stephanie Fischinger, Carolyn M. Boudreau, Joelle Brown, Jennifer H. Cooperrider, Jasneet Aneja, Todd. J. Suscovich, Barney S. Graham, Georg M. Lauer, Tessa Goetghebuer, Arnaud Marchant, Douglas Lauffenburger, Arthur Y. Kim, Laura E. Riley, and Galit Alter. 6/27/2019. “Fc glycan-mediated regulation of placental antibody transfer.” Cell Press, 178. Publisher's Version

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 toleragenic 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 towards NK cell-activating antibodies. This selective transfer was linked to di-galactosylated 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.

Last updated on 07/22/2019