Format

Send to

Choose Destination
Cell. 2019 Jun 27;178(1):202-215.e14. doi: 10.1016/j.cell.2019.05.044. Epub 2019 Jun 13.

Fc Glycan-Mediated Regulation of Placental Antibody Transfer.

Author information

1
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
2
Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA 02114, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Gastroenterology Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
5
Vaccine Research Center, National Institute of Allergy and Infectious Disease, Bethesda, MD 20892, USA.
6
Department of Pediatrics, Hôpital Saint-Pierre, Brussels 1000, Belgium.
7
Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi 6041, Belgium.
8
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Center for Gynepathology Research, Cambridge, MA 02139, USA.
9
Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA.
10
Department of Obstetrics and Gynecology, New York Presbyterian/Weill Cornell Medical Center, New York, NY 10065, USA. Electronic address: lar9110@med.cornell.edu.
11
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.

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.

KEYWORDS:

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

PMID:
31204102
PMCID:
PMC6741440
[Available on 2020-06-27]
DOI:
10.1016/j.cell.2019.05.044

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center