Compromised SARS-CoV-2-specific placental antibody transfer

Caroline Atyeo; Krista M Pullen; Evan A Bordt; Stephanie Fischinger; John Burke; Ashlin Michell; Matthew D Slein; Carolin Loos; Lydia L Shook; Adeline A Boatin; Laura J Yockey; David Pepin; Marie-Charlotte Meinsohn; Ngoc Minh Phuong Nguyen; Maeva Chauvin; Drucilla Roberts; Ilona T Goldfarb; Juan D Matute; Kaitlyn E James; Lael M Yonker; Lisa M Bebell; Anjali J Kaimal; Kathryn J Gray; Douglas Lauffenburger; Andrea G Edlow; Galit Alter

doi:10.1016/j.cell.2020.12.027

Compromised SARS-CoV-2-specific placental antibody transfer

Cell. 2021 Feb 4;184(3):628-642.e10. doi: 10.1016/j.cell.2020.12.027. Epub 2020 Dec 23.

Authors

Caroline Atyeo¹, Krista M Pullen², Evan A Bordt³, Stephanie Fischinger⁴, John Burke⁵, Ashlin Michell⁵, Matthew D Slein⁵, Carolin Loos⁶, Lydia L Shook⁷, Adeline A Boatin⁷, Laura J Yockey⁸, David Pepin⁹, Marie-Charlotte Meinsohn⁹, Ngoc Minh Phuong Nguyen⁹, Maeva Chauvin⁹, Drucilla Roberts¹⁰, Ilona T Goldfarb⁷, Juan D Matute¹¹, Kaitlyn E James⁷, Lael M Yonker¹¹, Lisa M Bebell¹², Anjali J Kaimal⁷, Kathryn J Gray¹³, Douglas Lauffenburger², Andrea G Edlow¹⁴, Galit Alter¹⁵

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA.
² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; PhD Program in Immunology and Virology, University of Duisburg-Essen, Essen 47057, Germany.
⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
⁶ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁸ Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁹ Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
¹⁰ Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
¹¹ Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
¹² Division of Infectious Diseases, Massachusetts General Hospital, MGH Global Health, and Harvard Medical School, Boston, MA 02114, USA.
¹³ Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
¹⁴ Department of Obstetrics, Gynecology and Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: aedlow@mgh.harvard.edu.
¹⁵ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: galter@mgh.harvard.edu.

Abstract

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

Keywords: Fc-receptor; SARS-CoV-2; antibodies; fucose; glycosylation; hypergammablobulinemia; infection; inflammation; placental transfer; pregnancy; trimester.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Viral / immunology*
COVID-19 / immunology*
Female
Humans
Immunoglobulin G / immunology*
Infant, Newborn
Maternal-Fetal Exchange / immunology*
Placenta / immunology*
Pregnancy
Pregnancy Complications, Infectious / immunology*
Pregnancy Trimester, Third / immunology
Receptors, IgG / immunology
SARS-CoV-2 / immunology*
THP-1 Cells

Substances

Antibodies, Viral
FCGR3A protein, human
Immunoglobulin G
Receptors, IgG

Abstract

Publication types

MeSH terms

Substances

Grants and funding