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负载金纳米颗粒(GNPs)的树突状细胞携带 HIV 肽和甘露糖,可增强 HIV 特异性 T 细胞反应。

Loading dendritic cells with gold nanoparticles (GNPs) bearing HIV-peptides and mannosides enhance HIV-specific T cell responses.

机构信息

AIDS Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), HIV Vaccine Development in Catalonia (HIVACAT), Hospital Clínic de Barcelona, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Paseo Miramón 182, Donostia-San Sebastián, Spain; CIC biomaGUNE, Paseo de Miramón 182, Donostia-San Sebastián, Spain.

出版信息

Nanomedicine. 2018 Feb;14(2):339-351. doi: 10.1016/j.nano.2017.11.009. Epub 2017 Nov 20.

Abstract

Gold nanoparticles (GNPs) decorated with glycans ameliorate dendritic cells (DC) uptake, antigen-presentation and T-cells cross-talk, which are important aspects in vaccine design. GNPs allow for high antigen loading, DC targeting, lack of toxicity and are straightforward prepared and easy to handle. The present study aimed to assess the capacity of DC to process and present HIV-1-peptides loaded onto GNPs bearing high-mannoside-type oligosaccharides (P1@HM) to autologous T-cells from HIV-1 patients. The results showed that P1@HM increased HIV-specific CD4 and CD8 T-cell proliferation and induced highly functional cytokine secretion compared with HIV-peptides alone. P1@HM elicits a highly efficient secretion of pro-T1 cytokines and chemokines, a moderate production of pro-T2 and significant higher secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. Thus, co-delivery of HIV-1 antigens and HM by GNPs is an excellent vaccine delivery system inducing HIV-specific cellular immune responses in HIV+ patients, being a promising approach to improve anti-HIV-1 vaccines.

摘要

金纳米颗粒(GNPs)表面修饰聚糖可改善树突状细胞(DC)摄取、抗原呈递和 T 细胞交叉对话的能力,这些都是疫苗设计的重要方面。GNPs 允许高抗原负载、靶向 DC、无毒性,并且易于制备和处理。本研究旨在评估负载高甘露糖型寡糖(P1@HM)的 GNPs 处理和呈递 HIV-1 肽以刺激来自 HIV-1 患者的自体 T 细胞的能力。结果表明,与 HIV 肽单独相比,P1@HM 增加了 HIV 特异性 CD4 和 CD8 T 细胞的增殖,并诱导了高度功能性的细胞因子分泌。P1@HM 引发了高效的前 T1 细胞因子和趋化因子的分泌,适度的前 T2 细胞因子的产生和显著更高的促炎细胞因子如 TNF-α和 IL-1β的分泌。因此,GNPs 共递送 HIV-1 抗原和 HM 是一种诱导 HIV 特异性细胞免疫应答的优秀疫苗递送系统,为改善抗 HIV-1 疫苗提供了一种有前途的方法。

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