Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has bee...

Descripción completa

Detalles Bibliográficos
Autores: Astorga-Gamaza, Antonio, Vitali, Michele, Borrajo, Mireya L., Suárez-López, Rosa, Jaime, Carlos, Bastús, Neus G., Serra-Peinado, Carla, Luque-Ballesteros, Laura, Blanch-Lombarte, Óscar, Prado, Julia G., Lorente, Juan, Pumarola, Félix, Pellicer, Marc, Falcó, Vicenç, Buzón, María J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/252925
Acceso en línea:http://hdl.handle.net/10261/252925
Access Level:acceso abierto
id ES_7ea8b6f2e87ed4fdf24ec6fc1002ee36
oai_identifier_str oai:digital.csic.es:10261/252925
network_acronym_str ES
network_name_str España
repository_id_str
spelling Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cellsAstorga-Gamaza, AntonioVitali, MicheleBorrajo, Mireya L.Suárez-López, RosaJaime, CarlosBastús, Neus G.Serra-Peinado, CarlaLuque-Ballesteros, LauraBlanch-Lombarte, ÓscarPrado, Julia G.Lorente, JuanPumarola, FélixPellicer, MarcFalcó, VicençBuzón, María J.HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), American National Institutes of Health (grant R21AI118411 to M.B), an unrestricted research grant from Bristol-Myers Squibb S.A.U (PfC-2015-AI424-564) to M.B, the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470) to M.G and the Spanish “Ministerio de Economía y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI14/01058) to J.G.P, a research grant from Gilead Sciences (GLD17-00204 and GLD19-00084) to M.B, GeSIDA and the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” (RD16/0025/0007). The Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179) to M.B and J.G.P (CPII15/00014). The “Pla estratègic de recerca i innovació en salut” (PERIS), from the Catalan Government to M.G. The Spanish Secretariat of Science and Innovation Ph.D. fellowship to A.A-G (BES-2016-076382), AGAUR-FI-B-00582 Ph.D. fellowship from the Catalan Government to O.BL, and PIF-UAB Ph.D. fellowship from Universitat Autònoma de Barcelona to R.SL.Peer reviewedElsevierMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionNational Institutes of Health (US)Bristol-Myers SquibbInstituto de Salud Carlos IIIGilead SciencesGeneralitat de CatalunyaUniversidad Autónoma de BarcelonaRed Española de Investigación en SIDAConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202120212021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/252925reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-67334-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-101082-B-I00https://doi.org/10.1016/j.nantod.2020.101056Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2529252026-05-22T06:33:51Z
dc.title.none.fl_str_mv Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
title Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
spellingShingle Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
Astorga-Gamaza, Antonio
title_short Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
title_full Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
title_fullStr Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
title_full_unstemmed Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
title_sort Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
dc.creator.none.fl_str_mv Astorga-Gamaza, Antonio
Vitali, Michele
Borrajo, Mireya L.
Suárez-López, Rosa
Jaime, Carlos
Bastús, Neus G.
Serra-Peinado, Carla
Luque-Ballesteros, Laura
Blanch-Lombarte, Óscar
Prado, Julia G.
Lorente, Juan
Pumarola, Félix
Pellicer, Marc
Falcó, Vicenç
Buzón, María J.
author Astorga-Gamaza, Antonio
author_facet Astorga-Gamaza, Antonio
Vitali, Michele
Borrajo, Mireya L.
Suárez-López, Rosa
Jaime, Carlos
Bastús, Neus G.
Serra-Peinado, Carla
Luque-Ballesteros, Laura
Blanch-Lombarte, Óscar
Prado, Julia G.
Lorente, Juan
Pumarola, Félix
Pellicer, Marc
Falcó, Vicenç
Buzón, María J.
author_role author
author2 Vitali, Michele
Borrajo, Mireya L.
Suárez-López, Rosa
Jaime, Carlos
Bastús, Neus G.
Serra-Peinado, Carla
Luque-Ballesteros, Laura
Blanch-Lombarte, Óscar
Prado, Julia G.
Lorente, Juan
Pumarola, Félix
Pellicer, Marc
Falcó, Vicenç
Buzón, María J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
European Commission
National Institutes of Health (US)
Bristol-Myers Squibb
Instituto de Salud Carlos III
Gilead Sciences
Generalitat de Catalunya
Universidad Autónoma de Barcelona
Red Española de Investigación en SIDA
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/252925
url http://hdl.handle.net/10261/252925
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-67334-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-101082-B-I00
https://doi.org/10.1016/j.nantod.2020.101056

dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411751939801088
score 15,811543