TY - JOUR
T1 - Antibody attributes, Fc receptor expression, gestation and maternal SARS-CoV-2 infection modulate HSV IgG placental transfer
AU - Mahant, Aakash Mahant
AU - Trejo, Fatima Estrada
AU - Aguilan, Jennifer T.
AU - Sidoli, Simone
AU - Permar, Sallie R.
AU - Herold, Betsy C.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/9/15
Y1 - 2023/9/15
N2 - 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.
AB - 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.
KW - Cell biology
KW - Immunology
KW - Physiology
KW - Virology
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U2 - 10.1016/j.isci.2023.107648
DO - 10.1016/j.isci.2023.107648
M3 - Article
AN - SCOPUS:85168853535
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 9
M1 - 107648
ER -