The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios

Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic...

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Autores: Sanchez-Merino, Victor, Martin-Serrano, Miguel, Beltran, Manuela, Lazaro-Martin, Beatriz, Cervantes, Eloísa, Oltra, Manuel, Sainz, Talia, García, Felipe, Navarro, Maria Luisa, Yuste, Eloisa
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26593
Acceso en línea:https://hdl.handle.net/20.500.12105/26593
Access Level:acceso abierto
Palabra clave:ART
HIV-1
Broadly neutralizing antibodies
Children
Undetectable viremia
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spelling The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ RatiosSanchez-Merino, VictorMartin-Serrano, MiguelBeltran, ManuelaLazaro-Martin, BeatrizCervantes, EloísaOltra, ManuelSainz, TaliaGarcía, FelipeNavarro, Maria LuisaYuste, EloisaARTHIV-1Broadly neutralizing antibodiesChildrenUndetectable viremiaBroadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.Multidisciplinary Digital Publishing Institute (MDPI)Instituto de Salud Carlos IIIRETICS-Sida (RIS-ISCIII) (España)Plan Nacional de I+D+i (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Ministerio de Ciencia e Innovación (España)Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)Fundación Banco SantanderFundación Universidad Alfonso X el Sabio20252025-03-3120242024-01-0120242024-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/26593reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES RD16CIII 0002ES PI20CIII 00039ES MPY315 20open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/265932026-06-12T12:43:37Z
dc.title.none.fl_str_mv The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
title The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
spellingShingle The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
Sanchez-Merino, Victor
ART
HIV-1
Broadly neutralizing antibodies
Children
Undetectable viremia
title_short The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
title_full The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
title_fullStr The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
title_full_unstemmed The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
title_sort The Association of HIV-1 Neutralization in Aviremic Children and Adults with Time to ART Initiation and CD4+/CD8+ Ratios
dc.creator.none.fl_str_mv Sanchez-Merino, Victor
Martin-Serrano, Miguel
Beltran, Manuela
Lazaro-Martin, Beatriz
Cervantes, Eloísa
Oltra, Manuel
Sainz, Talia
García, Felipe
Navarro, Maria Luisa
Yuste, Eloisa
author Sanchez-Merino, Victor
author_facet Sanchez-Merino, Victor
Martin-Serrano, Miguel
Beltran, Manuela
Lazaro-Martin, Beatriz
Cervantes, Eloísa
Oltra, Manuel
Sainz, Talia
García, Felipe
Navarro, Maria Luisa
Yuste, Eloisa
author_role author
author2 Martin-Serrano, Miguel
Beltran, Manuela
Lazaro-Martin, Beatriz
Cervantes, Eloísa
Oltra, Manuel
Sainz, Talia
García, Felipe
Navarro, Maria Luisa
Yuste, Eloisa
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
RETICS-Sida (RIS-ISCIII) (España)
Plan Nacional de I+D+i (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ministerio de Ciencia e Innovación (España)
Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas)
Fundación Banco Santander
Fundación Universidad Alfonso X el Sabio
dc.subject.none.fl_str_mv ART
HIV-1
Broadly neutralizing antibodies
Children
Undetectable viremia
topic ART
HIV-1
Broadly neutralizing antibodies
Children
Undetectable viremia
description Broadly neutralizing antibodies (bnAbs) bind and neutralize diverse HIV isolates and demonstrate protective effects in primate models and humans against specific isolates. To develop an effective HIV vaccine, it is widely believed that inducing these antibodies is crucial. However, the high somatic hypermutation in bnAbs and the limited affinity of HIV Env proteins for bnAb germline precursors suggest that extended antigen exposure is necessary for their production. Consequently, HIV vaccine research is exploring complex sequential vaccination strategies to guide the immune response through maturation stages. In this context, the exploration of the factors linked to the generation of these antibodies across diverse age groups becomes critical. In this study, we assessed the anti-HIV-1 neutralization potency and breadth in 108 aviremic adults and 109 aviremic children under 15 years of age who were receiving ART. We used a previously described minipanel of recombinant viruses and investigated the factors associated with neutralization in these individuals. We identified individuals in both groups who were capable of neutralizing viruses from three different subtypes, with greater cross-neutralization observed in the adult group (49.0% vs. 9.2%). In both groups, we observed an inverse association between neutralization breadth and the CD4+/CD8+ ratio, as well as a direct association with the time to ART initiation. However, we found no association with time post-infection, cumulative ART duration, or CD8+ cell levels. The present study demonstrates that children receiving antiretroviral therapy generate broadly neutralizing responses to HIV-1, albeit with lower magnitude compared to adults. We also observed that neutralization breadth is associated with CD4+/CD8+ levels and time to treatment initiation in both children and adults living with HIV-1. Our interpretation of these results is that a delay in ART initiation could have prolonged the antigenic stimulation associated with viral replication and thus facilitate the capacity to elicit long-lasting broadly neutralizing responses. These results corroborate prior findings that show that HIV-1-neutralizing responses can persist for years, even at low antigen levels, implying an HIV-1 vaccine may induce lasting neutralizing antibody response.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
2024
2024-01-01
2025
2025-03-31
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26593
url https://hdl.handle.net/20.500.12105/26593
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES RD16CIII 0002
ES PI20CIII 00039
ES MPY315 20
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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