Fc Glycan-Mediated Regulation of Placental Antibody Transfer

Madeleine F. Jennewein, Ilona Goldfarb, Sepideh Dolatshahi, Patrick Gerard 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 LauffenburgerArthur Y. Kim, Laura E. Riley*, Galit Alter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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. Antibodies with a specific glycan modification and with the ability to activate NK cells are selectively transferred across the placenta to the neonate.

Original languageEnglish (US)
Pages (from-to)202-215.e14
JournalCell
Volume178
Issue number1
DOIs
StatePublished - Jun 27 2019

Keywords

  • ADCC
  • antibody functionality
  • antibody glycosylation
  • maternal vaccination
  • neonatal immunology
  • trans-placental transfer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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