Antibody attributes, Fc receptor expression, gestation and maternal SARS-CoV-2 infection modulate HSV IgG placental transfer

Aakash Mahant Mahant; Fatima Estrada Trejo; Jennifer T Aguilan; Simone Sidoli; Sallie R Permar; Betsy C Herold

doi:10.1016/j.isci.2023.107648

Antibody attributes, Fc receptor expression, gestation and maternal SARS-CoV-2 infection modulate HSV IgG placental transfer

iScience. 2023 Aug 15;26(9):107648. doi: 10.1016/j.isci.2023.107648. eCollection 2023 Sep 15.

Authors

Aakash Mahant Mahant¹, Fatima Estrada Trejo¹, Jennifer T Aguilan¹, Simone Sidoli¹, Sallie R Permar², Betsy C Herold¹

Affiliations

¹ Departments of Microbiology and Immunology, Obstetrics-Gynecology and Women's Health, and Biochemistry Albert Einstein College of Medicine, Bronx, NY 10461, USA.
² Department of Pediatrics, Weil Cornell Medicine, New York, NY 10021, USA.

Abstract

Antibody-dependent cellular cytotoxicity (ADCC) is associated with protection against neonatal herpes. We hypothesized that placental transfer of ADCC-mediating herpes simplex virus (HSV) immunoglobulin G (IgG) is influenced by antigenic target, function, glycans, gestational age, and maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Maternal and cord blood were collected from HSV-seropositive (HSV+) mothers pre-COVID and HSV+/SARS-CoV-2+ mothers during the pandemic. Transfer of HSV neutralizing IgG was significantly lower in preterm versus term dyads (transfer ratio [TR] 0.84 vs. 2.44) whereas the TR of ADCC-mediating IgG was <1.0 in both term and preterm pre-COVID dyads. Anti-glycoprotein D IgG, which had only neutralizing activity, and anti-glycoprotein B (gB) IgG, which displayed neutralizing and ADCC activity, exhibited different relative affinities for the neonatal Fc receptor (FcRn) and expressed different glycans. The transfer of ADCC-mediating IgG increased significantly in term SARS-CoV-2+ dyads. This was associated with greater placental colocalization of FcRn with FcγRIIIa. These findings have implications for strategies to prevent neonatal herpes.

Keywords: Cell biology; Immunology; Physiology; Virology.