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聚合介导的抗原呈递。

Polymerization-Mediated Antigen Presentation.

机构信息

Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

College of Material, Chemistry and Chemical Engineering, Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Key Laboratory of Organosilicon Material Technology, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.

出版信息

J Am Chem Soc. 2023 Jun 21;145(24):13261-13272. doi: 10.1021/jacs.3c02682. Epub 2023 Jun 1.

Abstract

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, polymerization-mediated antigen presentation (IPAP) is described, in which antigen-loaded nanovaccines are spontaneously formed and efficiently anchored onto the surface of dendritic cells 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.

摘要

激活抗原呈递细胞对于产生适应性免疫至关重要,然而由于抗原特异性启动不理想,传统的激活策略的效果仍不尽人意。在这里,描述了聚合介导的抗原呈递(IPAP),其中负载抗原的纳米疫苗通过与多巴胺共沉积自动形成并有效地锚定在树突状细胞的表面。由此产生的化学结合的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时间,并增强随后在引流淋巴结中的积累,从而引发强烈的抗原特异性细胞和体液免疫反应。IPAP 也适用于不同的抗原,并且能够避免复杂的制备和纯化的缺点。通过实施卵清蛋白,IPAP 在预防性小鼠模型中诱导针对过表达卵清蛋白的肿瘤细胞挑战的显著保护性免疫。使用 SARS-CoV-2 刺突蛋白 S1 亚基也显著增加了小鼠中 S1 特异性免疫球蛋白 G 的产生。IPAP 为刺激抗原呈递细胞以增强抗原特异性适应性反应提供了一种独特的策略,并提出了一种针对各种疾病的简便而通用的免疫接种方法。

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