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

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Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells
Nano Today ( IF 13.2 ) Pub Date : 2020-12-20 , DOI: 10.1016/j.nantod.2020.101056
Antonio Astorga-Gamaza ₁ , Michele Vitali ₁ , Mireya L Borrajo ₁ , Rosa Suárez-López ₂ , Carlos Jaime ₂ , Neus Bastus _{3,

4} , Carla Serra-Peinado ₁ , Laura Luque-Ballesteros ₁ , Oscar Blanch-Lombarte _{5,

6} , Julia G Prado _{5,

6} , Juan Lorente ₇ , Felix Pumarola ₇ , Marc Pellicer ₇ , Vicenç Falcó ₁ , Meritxell Genescà ₁ , Víctor Puntes _{1,

3,

4} , Maria J Buzon ₁

Affiliation

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.

中文翻译：

AuNPs 上的抗体协同吸附及其迫使自然杀伤细胞杀死 HIV 感染的 T 细胞

HIV 是一种持续感染，会对免疫系统产生负面影响。需要新的工具来重振不同免疫细胞群以影响艾滋病毒。在此，开发了一种新型纳米工具，用于特异性增强对 HIV 感染的 T 细胞的自然杀伤 (NK) 免疫反应。双特异性金纳米颗粒 (BiAb-AuNPs) 与 IgG 抗 HIVgp120 和 IgG 抗人 CD16 抗体双重偶联，是通过一种新的受控、无接头和协作偶联方法生成的，可促进域中抗体的有序分布和分离。协同吸附的抗体完全保留了识别其同源抗原的能力，并且能够显着增强表达 HIV 的细胞和 NK 细胞之间的细胞间接触。结果，BiAb-AuNPs 引发了针对血液和人扁桃体外植体中感染 HIV 的细胞的有效细胞毒性反应。值得注意的是，在 HIV 潜伏原代细胞模型中，BiAb-AuNP 能够显着减少病毒重新激活后的潜伏 HIV 感染。这种新颖的分子靶向策略使用双特异性纳米工具来增强免疫系统，代表了一种新的近似方法，具有除艾滋病毒之外的潜在应用。

更新日期：2020-12-20

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