Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques

Autores
Moog, C; Dereuddre Bosquet, N; Teillaud, J-L; Biedma, Marina Elizabeth; Holl, V; Van Ham, G; Heyndrickx, L; Van Dorsselaer, A; Katinger, D; Vcelar, B; Zolla Pazner, S; Mangeot, I; Kelly, C; Shattock, R. J.; Le Grand, R
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcc receptor (FccR)–mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FccR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.
Fil: Moog, C. Institute of Virology. Strasbourg; Francia
Fil: Dereuddre Bosquet, N. Universite Paris Sud; Francia
Fil: Teillaud, J-L. Paris Descartes University; Francia
Fil: Biedma, Marina Elizabeth. Institute of Virology. Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Holl, V. Hematology and Flow Department. Ginebra; Suiza
Fil: Van Ham, G. Universidad de Amberes; Bélgica
Fil: Heyndrickx, L. Universidad de Amberes; Bélgica
Fil: Van Dorsselaer, A. UMR 7178; Francia
Fil: Katinger, D. Polymun Scientific GmbH; Alemania
Fil: Vcelar, B. Polymun Scientific GmbH; Alemania
Fil: Zolla Pazner, S. School of Medicine and New York Veterans Affairs Medical Center; Estados Unidos
Fil: Mangeot, I. Universite Paris Sud; Francia
Fil: Kelly, C. King's College; Reino Unido
Fil: Shattock, R. J.. Imperial College London; Reino Unido
Fil: Le Grand, R. Universite Paris Sud; Francia
Materia
Antibody-Mediated Inhibition
Nhp
Vaginal Shiv Challenge
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/29547
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/29547
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaquesMoog, CDereuddre Bosquet, NTeillaud, J-LBiedma, Marina ElizabethHoll, VVan Ham, GHeyndrickx, LVan Dorsselaer, AKatinger, DVcelar, BZolla Pazner, SMangeot, IKelly, CShattock, R. J.Le Grand, RAntibody-Mediated InhibitionNhpVaginal Shiv Challengehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcc receptor (FccR)–mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FccR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.Fil: Moog, C. Institute of Virology. Strasbourg; FranciaFil: Dereuddre Bosquet, N. Universite Paris Sud; FranciaFil: Teillaud, J-L. Paris Descartes University; FranciaFil: Biedma, Marina Elizabeth. Institute of Virology. Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Holl, V. Hematology and Flow Department. Ginebra; SuizaFil: Van Ham, G. Universidad de Amberes; BélgicaFil: Heyndrickx, L. Universidad de Amberes; BélgicaFil: Van Dorsselaer, A. UMR 7178; FranciaFil: Katinger, D. Polymun Scientific GmbH; AlemaniaFil: Vcelar, B. Polymun Scientific GmbH; AlemaniaFil: Zolla Pazner, S. School of Medicine and New York Veterans Affairs Medical Center; Estados UnidosFil: Mangeot, I. Universite Paris Sud; FranciaFil: Kelly, C. King's College; Reino UnidoFil: Shattock, R. J.. Imperial College London; Reino UnidoFil: Le Grand, R. Universite Paris Sud; FranciaNature Publishing Group2014-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/29547Moog, C; Dereuddre Bosquet, N; Teillaud, J-L; Biedma, Marina Elizabeth; Holl, V; et al.; Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques; Nature Publishing Group; Mucosal Immunology; 7; 1; 1-2014; 46-561933-0219CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/mi201323info:eu-repo/semantics/altIdentifier/doi/10.1038/mi.2013.23info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:28:12Zoai:ri.conicet.gov.ar:11336/29547instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:28:13.204CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
title Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
spellingShingle Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
Moog, C
Antibody-Mediated Inhibition
Nhp
Vaginal Shiv Challenge
title_short Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
title_full Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
title_fullStr Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
title_full_unstemmed Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
title_sort Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques
dc.creator.none.fl_str_mv Moog, C
Dereuddre Bosquet, N
Teillaud, J-L
Biedma, Marina Elizabeth
Holl, V
Van Ham, G
Heyndrickx, L
Van Dorsselaer, A
Katinger, D
Vcelar, B
Zolla Pazner, S
Mangeot, I
Kelly, C
Shattock, R. J.
Le Grand, R
author Moog, C
author_facet Moog, C
Dereuddre Bosquet, N
Teillaud, J-L
Biedma, Marina Elizabeth
Holl, V
Van Ham, G
Heyndrickx, L
Van Dorsselaer, A
Katinger, D
Vcelar, B
Zolla Pazner, S
Mangeot, I
Kelly, C
Shattock, R. J.
Le Grand, R
author_role author
author2 Dereuddre Bosquet, N
Teillaud, J-L
Biedma, Marina Elizabeth
Holl, V
Van Ham, G
Heyndrickx, L
Van Dorsselaer, A
Katinger, D
Vcelar, B
Zolla Pazner, S
Mangeot, I
Kelly, C
Shattock, R. J.
Le Grand, R
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antibody-Mediated Inhibition
Nhp
Vaginal Shiv Challenge
topic Antibody-Mediated Inhibition
Nhp
Vaginal Shiv Challenge
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcc receptor (FccR)–mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FccR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.
Fil: Moog, C. Institute of Virology. Strasbourg; Francia
Fil: Dereuddre Bosquet, N. Universite Paris Sud; Francia
Fil: Teillaud, J-L. Paris Descartes University; Francia
Fil: Biedma, Marina Elizabeth. Institute of Virology. Strasbourg; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Holl, V. Hematology and Flow Department. Ginebra; Suiza
Fil: Van Ham, G. Universidad de Amberes; Bélgica
Fil: Heyndrickx, L. Universidad de Amberes; Bélgica
Fil: Van Dorsselaer, A. UMR 7178; Francia
Fil: Katinger, D. Polymun Scientific GmbH; Alemania
Fil: Vcelar, B. Polymun Scientific GmbH; Alemania
Fil: Zolla Pazner, S. School of Medicine and New York Veterans Affairs Medical Center; Estados Unidos
Fil: Mangeot, I. Universite Paris Sud; Francia
Fil: Kelly, C. King's College; Reino Unido
Fil: Shattock, R. J.. Imperial College London; Reino Unido
Fil: Le Grand, R. Universite Paris Sud; Francia
description Definition of antibody (Ab) functions capable of preventing mucosal HIV transmission may be critical to both effective vaccine development and the prophylactic use of monoclonal Abs. Although direct antibody-mediated neutralization is highly effective against cell-free virus, increasing evidence suggests an important role for immunoglobulin G (IgG) Fcc receptor (FccR)–mediated inhibition of HIV replication. Thus, a panel of well-known neutralizing (NAbs) and nonneutralizing Abs (NoNAbs) were screened for their ability to block HIV acquisition and replication in vitro in either an independent or FccR-dependent manner. Abs displaying the highest Fc-mediated inhibitory activity in various in vitro assays were selected, formulated for topical vaginal application in a microbicide gel, and tested for their antiviral activity against SHIVSF162P3 vaginal challenge in non-human primates (NHPs). A combination of three NAbs, 2G12, 2F5, and 4E10, fully prevented simian/human immunodeficiency virus (SHIV) vaginal transmission in 10 out of 15 treated NHPs, whereas a combination of two NoNAbs, 246-D and 4B3, although having no impact on SHIV acquisition, reduced plasma viral load. These results indicate that anti-HIV Abs with distinct neutralization and inhibitory functions differentially affect in vivo HIV acquisition and replication, by interfering with early viral replication and dissemination. Therefore, combining diverse Ab properties may potentiate the protective effects of anti-HIV-Ab-based strategies.
publishDate 2014
dc.date.none.fl_str_mv 2014-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/29547
Moog, C; Dereuddre Bosquet, N; Teillaud, J-L; Biedma, Marina Elizabeth; Holl, V; et al.; Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques; Nature Publishing Group; Mucosal Immunology; 7; 1; 1-2014; 46-56
1933-0219
CONICET Digital
CONICET
url http://hdl.handle.net/11336/29547
identifier_str_mv Moog, C; Dereuddre Bosquet, N; Teillaud, J-L; Biedma, Marina Elizabeth; Holl, V; et al.; Protective effect of vaginal application of neutralizing and non-neutralizing inhibitory antibodies against vaginal HIV challenge in macaques; Nature Publishing Group; Mucosal Immunology; 7; 1; 1-2014; 46-56
1933-0219
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/mi201323
info:eu-repo/semantics/altIdentifier/doi/10.1038/mi.2013.23
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.221938

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