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...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| 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 |
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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 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Elsevier |
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Elsevier |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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