TY - JOUR
T1 - Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
AU - Barrows, Brittani M.
AU - Krebs, Shelly J.
AU - Jian, Ningbo
AU - Zemil, Michelle
AU - Slike, Bonnie M.
AU - Dussupt, Vincent
AU - Tran, Ursula
AU - Mendez-Rivera, Letzibeth
AU - Chang, David
AU - O’Sullivan, Anne Marie
AU - Mann, Brendan
AU - Sanders-Buell, Eric
AU - Shubin, Zhanna
AU - Creegan, Matt
AU - Paquin-Proulx, Dominic
AU - Ehrenberg, Philip
AU - Laurence-Chenine, Agnes
AU - Srithanaviboonchai, Kriengkrai
AU - Thomas, Rasmi
AU - Eller, Michael A.
AU - Ferrari, Guido
AU - Robb, Merlin
AU - Rao, Venigalla
AU - Tovanabutra, Sodsai
AU - Polonis, Victoria R.
AU - Wieczorek, Lindsay
N1 - Publisher Copyright:
Copyright © 2022 Barrows, Krebs, Jian, Zemil, Slike, Dussupt, Tran, Mendez-Rivera, Chang, O’Sullivan, Mann, Sanders-Buell, Shubin, Creegan, Paquin-Proulx, Ehrenberg, Laurence-Chenine, Srithanaviboonchai, Thomas, Eller, Ferrari, Robb, Rao, Tovanabutra, Polonis and Wieczorek.
PY - 2022/12/12
Y1 - 2022/12/12
N2 - Introduction: Infants acquire maternal antibodies by Fc receptor transcytosis across the placenta during pregnancy. Fc receptors are expressed on immune cells and are important for activation of effector cell functions. Methods: In this study, we evaluated Fc receptor engagement and ADCC activity of plasma binding antibodies from human immunodeficiency virus-1 (HIV) -infected mothers and to identify factors that may contribute to protection from HIV vertical transmission. Results: HIV-specific binding and Fc receptor engagement of plasma antibodies varied between mothers by transmission status and infants by infection status. Non-transmitting (NT) mothers and HIV-uninfected infants had antibodies with higher neonatal Fc receptor (FcRn) and FcγR engagement, as compared to transmitting (T) mothers and HIV+ infants, respectively. A significant inverse correlation between plasma antibody FcRn and FcγR engagement was observed for T mothers, but not NT mothers. Conversely, a significant direct correlation was observed between plasma antibody FcRn and FcγR engagement for HIV- infants, but not for HIV+ infants. Consequently, we observed significantly higher plasma antibody ADCC potency and breadth in HIV- infants, as compared to HIV+ infants. However, no differences in overall ADCC potency and breadth were observed between mothers. FcRn-engagement of HIV-specific antibodies in both mothers and infants predicted a lack of vertical transmission of HIV. Discussion: This study indicates that HIV-uninfected infants acquire HIV-specific antibodies with greater Fc receptor engagement and thus, greater ADCC capacity.
AB - Introduction: Infants acquire maternal antibodies by Fc receptor transcytosis across the placenta during pregnancy. Fc receptors are expressed on immune cells and are important for activation of effector cell functions. Methods: In this study, we evaluated Fc receptor engagement and ADCC activity of plasma binding antibodies from human immunodeficiency virus-1 (HIV) -infected mothers and to identify factors that may contribute to protection from HIV vertical transmission. Results: HIV-specific binding and Fc receptor engagement of plasma antibodies varied between mothers by transmission status and infants by infection status. Non-transmitting (NT) mothers and HIV-uninfected infants had antibodies with higher neonatal Fc receptor (FcRn) and FcγR engagement, as compared to transmitting (T) mothers and HIV+ infants, respectively. A significant inverse correlation between plasma antibody FcRn and FcγR engagement was observed for T mothers, but not NT mothers. Conversely, a significant direct correlation was observed between plasma antibody FcRn and FcγR engagement for HIV- infants, but not for HIV+ infants. Consequently, we observed significantly higher plasma antibody ADCC potency and breadth in HIV- infants, as compared to HIV+ infants. However, no differences in overall ADCC potency and breadth were observed between mothers. FcRn-engagement of HIV-specific antibodies in both mothers and infants predicted a lack of vertical transmission of HIV. Discussion: This study indicates that HIV-uninfected infants acquire HIV-specific antibodies with greater Fc receptor engagement and thus, greater ADCC capacity.
KW - antibody dependent cellular cytotoxicity
KW - CRF01_AE HIV
KW - neonatal Fc receptor
KW - passive immunity
KW - pregnancy
KW - protective immunity
KW - Thailand
KW - vertical transmission
UR - https://www.scopus.com/pages/publications/85144986471
U2 - 10.3389/fimmu.2022.1051501
DO - 10.3389/fimmu.2022.1051501
M3 - Article
C2 - 36578481
AN - SCOPUS:85144986471
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1051501
ER -