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...

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Detalhes bibliográficos
Autores: Astorga-Gamaza, Antonio|||0000-0002-1276-5276, Vitali, Michele|||0000-0001-8618-8988, Borrajo, Mireya L., Suárez-López, Rosa, Jaime, Carlos|||0000-0002-9690-9053, Bastús, Neus G.|||0000-0002-3144-7986, Serra-Peinado, Carla|||0000-0003-1413-3990, Luque-Ballesteros, Laura|||0000-0001-9515-5889, Blanch-Lombarte, Oscar|||0000-0002-8317-7535, Prado, Julia G.|||0000-0002-5439-4645, Lorente Guerrero, Juan|||0000-0002-3264-0251, Pumarola, Felix|||0000-0002-7914-1695, Pellicer, Marc, Falcó, Vicenç|||0000-0001-9626-0023, Genescà Ferrer, Meritxell|||0000-0001-6413-3812, Puntes, Víctor|||0000-0001-8996-9499, Buzón, Maria José|||0000-0003-4427-9413
Formato: artículo
Fecha de publicación:2021
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:268436
Acesso em linha:https://ddd.uab.cat/record/268436
https://dx.doi.org/urn:doi:10.1016/j.nantod.2020.101056
Access Level:acceso abierto
Palavra-chave:HIV
Bispecific nanoparticles
NK cells
Polarization
Descrição
Resumo: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.

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