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Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compa...

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Autores principales: Dispinseri, Stefania, Cavarelli, Mariangela, Tolazzi, Monica, Plebani, Anna Maria, Jansson, Marianne, Scarlatti, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999787/
https://www.ncbi.nlm.nih.gov/pubmed/33799407
http://dx.doi.org/10.3390/vaccines9030260
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author Dispinseri, Stefania
Cavarelli, Mariangela
Tolazzi, Monica
Plebani, Anna Maria
Jansson, Marianne
Scarlatti, Gabriella
author_facet Dispinseri, Stefania
Cavarelli, Mariangela
Tolazzi, Monica
Plebani, Anna Maria
Jansson, Marianne
Scarlatti, Gabriella
author_sort Dispinseri, Stefania
collection PubMed
description The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.
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spelling pubmed-79997872021-03-28 Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children Dispinseri, Stefania Cavarelli, Mariangela Tolazzi, Monica Plebani, Anna Maria Jansson, Marianne Scarlatti, Gabriella Vaccines (Basel) Article The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children. MDPI 2021-03-14 /pmc/articles/PMC7999787/ /pubmed/33799407 http://dx.doi.org/10.3390/vaccines9030260 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Dispinseri, Stefania
Cavarelli, Mariangela
Tolazzi, Monica
Plebani, Anna Maria
Jansson, Marianne
Scarlatti, Gabriella
Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title_full Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title_fullStr Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title_full_unstemmed Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title_short Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children
title_sort continuous hiv-1 escape from autologous neutralization and development of cross-reactive antibody responses characterizes slow disease progression of children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999787/
https://www.ncbi.nlm.nih.gov/pubmed/33799407
http://dx.doi.org/10.3390/vaccines9030260
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