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Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission

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...

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Autores principales: Barrows, Brittani M., Krebs, Shelly J., Jian, Ningbo, Zemil, Michelle, Slike, Bonnie M., Dussupt, Vincent, Tran, Ursula, Mendez-Rivera, Letzibeth, Chang, David, O’Sullivan, Anne Marie, Mann, Brendan, Sanders-Buell, Eric, Shubin, Zhanna, Creegan, Matt, Paquin-Proulx, Dominic, Ehrenberg, Philip, Laurence-Chenine, Agnes, Srithanaviboonchai, Kriengkrai, Thomas, Rasmi, Eller, Michael A., Ferrari, Guido, Robb, Merlin, Rao, Venigalla, Tovanabutra, Sodsai, Polonis, Victoria R., Wieczorek, Lindsay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791209/
https://www.ncbi.nlm.nih.gov/pubmed/36578481
http://dx.doi.org/10.3389/fimmu.2022.1051501
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author Barrows, Brittani M.
Krebs, Shelly J.
Jian, Ningbo
Zemil, Michelle
Slike, Bonnie M.
Dussupt, Vincent
Tran, Ursula
Mendez-Rivera, Letzibeth
Chang, David
O’Sullivan, Anne Marie
Mann, Brendan
Sanders-Buell, Eric
Shubin, Zhanna
Creegan, Matt
Paquin-Proulx, Dominic
Ehrenberg, Philip
Laurence-Chenine, Agnes
Srithanaviboonchai, Kriengkrai
Thomas, Rasmi
Eller, Michael A.
Ferrari, Guido
Robb, Merlin
Rao, Venigalla
Tovanabutra, Sodsai
Polonis, Victoria R.
Wieczorek, Lindsay
author_facet Barrows, Brittani M.
Krebs, Shelly J.
Jian, Ningbo
Zemil, Michelle
Slike, Bonnie M.
Dussupt, Vincent
Tran, Ursula
Mendez-Rivera, Letzibeth
Chang, David
O’Sullivan, Anne Marie
Mann, Brendan
Sanders-Buell, Eric
Shubin, Zhanna
Creegan, Matt
Paquin-Proulx, Dominic
Ehrenberg, Philip
Laurence-Chenine, Agnes
Srithanaviboonchai, Kriengkrai
Thomas, Rasmi
Eller, Michael A.
Ferrari, Guido
Robb, Merlin
Rao, Venigalla
Tovanabutra, Sodsai
Polonis, Victoria R.
Wieczorek, Lindsay
author_sort Barrows, Brittani M.
collection PubMed
description 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.
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spelling pubmed-97912092022-12-27 Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission Barrows, Brittani M. Krebs, Shelly J. Jian, Ningbo Zemil, Michelle Slike, Bonnie M. Dussupt, Vincent Tran, Ursula Mendez-Rivera, Letzibeth Chang, David O’Sullivan, Anne Marie Mann, Brendan Sanders-Buell, Eric Shubin, Zhanna Creegan, Matt Paquin-Proulx, Dominic Ehrenberg, Philip Laurence-Chenine, Agnes Srithanaviboonchai, Kriengkrai Thomas, Rasmi Eller, Michael A. Ferrari, Guido Robb, Merlin Rao, Venigalla Tovanabutra, Sodsai Polonis, Victoria R. Wieczorek, Lindsay Front Immunol Immunology 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. Frontiers Media S.A. 2022-12-12 /pmc/articles/PMC9791209/ /pubmed/36578481 http://dx.doi.org/10.3389/fimmu.2022.1051501 Text en 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 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Barrows, Brittani M.
Krebs, Shelly J.
Jian, Ningbo
Zemil, Michelle
Slike, Bonnie M.
Dussupt, Vincent
Tran, Ursula
Mendez-Rivera, Letzibeth
Chang, David
O’Sullivan, Anne Marie
Mann, Brendan
Sanders-Buell, Eric
Shubin, Zhanna
Creegan, Matt
Paquin-Proulx, Dominic
Ehrenberg, Philip
Laurence-Chenine, Agnes
Srithanaviboonchai, Kriengkrai
Thomas, Rasmi
Eller, Michael A.
Ferrari, Guido
Robb, Merlin
Rao, Venigalla
Tovanabutra, Sodsai
Polonis, Victoria R.
Wieczorek, Lindsay
Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title_full Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title_fullStr Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title_full_unstemmed Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title_short Fc receptor engagement of HIV-1 Env-specific antibodies in mothers and infants predicts reduced vertical transmission
title_sort fc receptor engagement of hiv-1 env-specific antibodies in mothers and infants predicts reduced vertical transmission
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9791209/
https://www.ncbi.nlm.nih.gov/pubmed/36578481
http://dx.doi.org/10.3389/fimmu.2022.1051501
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