학술논문
Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
Document Type
article
Author
Brittani M. Barrows; Shelly J. Krebs; Ningbo Jian; Michelle Zemil; Bonnie M. Slike; Vincent Dussupt; Ursula Tran; Letzibeth Mendez-Rivera; David Chang; Anne Marie O’Sullivan; Brendan Mann; Eric Sanders-Buell; Zhanna Shubin; Matt Creegan; Dominic Paquin-Proulx; Philip Ehrenberg; Agnes Laurence-Chenine; Kriengkrai Srithanaviboonchai; Rasmi Thomas; Michael A. Eller; Guido Ferrari; Merlin Robb; Venigalla Rao; Sodsai Tovanabutra; Victoria R. Polonis; Lindsay Wieczorek
Source
Frontiers in Immunology, Vol 13 (2022)
Subject
Language
English
ISSN
1664-3224
Abstract
IntroductionInfants 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.MethodsIn 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.ResultsHIV-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.DiscussionThis study indicates that HIV-uninfected infants acquire HIV-specific antibodies with greater Fc receptor engagement and thus, greater ADCC capacity.