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In Situ Polymerization-Mediated Antigen Presentation
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-06-01 , DOI: 10.1021/jacs.3c02682
Chao Pan 1 , Lu Wang 1 , Mengmeng Zhang 1 , Juanjuan Li 1 , Junqiu Liu 2 , Jinyao Liu 1
Affiliation  

Activating antigen-presenting cells is essential to generate adaptive immunity, while the efficacy of conventional activation strategies remains unsatisfactory due to suboptimal antigen-specific priming. Here, in situ polymerization-mediated antigen presentation (IPAP) is described, in which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto the surface of dendritic cells in vivo through co-deposition with dopamine. The resulting chemically bound nanovaccines can promote antigen presentation by elevating macropinocytosis-based cell uptake and reducing lysosome-related antigen degradation. IPAP is able to prolong the duration of antigen reservation in the injection site and enhance subsequent accumulation in the draining lymph nodes, thereby eliciting robust antigen-specific cellular and humoral immune responses. IPAP is also applicable for different antigens and capable of circumventing the disadvantages of complicated preparation and purification. By implementation with ovalbumin, IPAP induces a significant protective immunity against ovalbumin-overexpressing tumor cell challenge in a prophylactic murine model. The use of the SARS-CoV-2 Spike protein S1 subunit also remarkably increases the production of S1-specific immunoglobulin G in mice. IPAP offers a unique strategy for stimulating antigen-presenting cells to boost antigen-specific adaptive responses and proposes a facile yet versatile method for immunization against various diseases.

中文翻译:

原位聚合介导的抗原呈递

激活抗原呈递细胞对于产生适应性免疫至关重要,而由于抗原特异性启动不理想,传统激活策略的功效仍然不能令人满意。在这里,描述了原位聚合介导的抗原呈递(IPAP),其中负载抗原的纳米疫苗在体内自发形成并有效地锚定到树突状细胞的表面上通过与多巴胺共沉积。由此产生的化学结合纳米疫苗可以通过提高基于巨胞饮作用的细胞摄取并减少溶酶体相关的抗原降解来促进抗原呈递。IPAP能够延长注射部位抗原保留的持续时间,并增强随后在引流淋巴结中的积累,从而引发强大的抗原特异性细胞和体液免疫反应。IPAP还适用于不同的抗原,并且能够克服制备和纯化复杂的缺点。通过与卵清蛋白一起实施,IPAP 在预防性小鼠模型中诱导针对卵清蛋白过度表达的肿瘤细胞攻击的显着保护性免疫。SARS-CoV-2 Spike 蛋白 S1 亚基的使用还显着增加了小鼠中 S1 特异性免疫球蛋白 G 的产生。IPAP 提供了一种刺激抗原呈递细胞以增强抗原特异性适应性反应的独特策略,并提出了一种针对各种疾病的简便而通用的免疫方法。
更新日期:2023-06-01
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