Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.
Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.
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DOI：
10.1080/09205063.2014.940243
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Narasimhan B
中科院分区：
文献类型：
--
作者：
Vela Ramirez JE;Roychoudhury R;Habte HH;Cho MW;Pohl NL;Narasimhan B
具有针对免疫细胞上特定受体的配体的聚合物纳米颗粒的功能化提供了通过赋予颗粒模仿病原体的属性来定制佐剂特性的机会。聚酐纳米粒子是有前途的疫苗佐剂，具有免疫调节、持续抗原释放、抗原呈递细胞激活和蛋白质抗原稳定等理想特性。由于树突状细胞和巨噬细胞在病毒传播中的重要作用，这些能力可用于设计针对病毒病原体（例如 HIV-1）的纳米疫苗。在这项工作中，开发了一种优化的工艺，用于 HIV-1 抗原负载的聚酸酐纳米颗粒的碳水化合物功能化。碳水化合物功能化的纳米颗粒在释放时保留了抗原特性，并且还能够实现持续的抗原释放动力学。据观察，颗粒内化具有化学依赖性，带正电荷的纳米颗粒被树突状细胞更有效地吸收。羧甲基-α-d-吡喃甘露糖基-(1,2)-d-吡喃甘露糖苷功能化纳米粒子证明了激活标志物 CD40 和 CD206 的上调。研究表明细胞因子 IL-6 和 TNF-α 的分泌依赖于碳水化合物功能化纳米粒子的刺激。这些结果为碳水化合物功能化纳米颗粒与抗原呈递细胞之间的相互作用提供了重要的新见解，并为合理设计针对 HIV-1 的靶向纳米疫苗提供了基础信息。
The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells, and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by dendritic cells. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and antigen presenting cells and provide foundational information for the rational design of targeted nanovaccines against HIV-1.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
9.7
作者：
Carrillo-Conde, Brenda R.;Ramer-Tait, Amanda E.;Narasimhan, Balaji
通讯作者：
Narasimhan, Balaji
影响因子：
5.4
作者：
Engering, AJ;Cella, M;Pieters, J
通讯作者：
Pieters, J
影响因子：
9.7
作者：
Carrillo-Conde, Brenda;Schiltz, Elise;Narasimhan, Balaji
通讯作者：
Narasimhan, Balaji
影响因子：
1.5
作者：
BUCHACHER, A;PREDL, R;KATINGER, H
通讯作者：
KATINGER, H