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一种基于壳聚糖/铝佐剂的呼吸道粘膜疫苗可诱导粘膜和全身免疫反应。

A respiratory mucosal vaccine based on chitosan/aluminum adjuvant induces both mucosal and systemic immune responses.

作者信息

Chen Ruitong, Nie Meifeng, Jiang Yuetong, Wu Shuyu, Wu Junwei, Qiu Dekui, Wu Yangtao, Yuan Quan, Wang Shaojuan, Jiang Yao, Zhang Tianying

机构信息

State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health (School of Life Science), Xiamen University, Xiamen, Fujian 351002, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, Fujian 361102, China.

State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health (School of Life Science), Xiamen University, Xiamen, Fujian 351002, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen, Fujian 361102, China.

出版信息

Int J Pharm. 2025 Feb 10;670:125168. doi: 10.1016/j.ijpharm.2025.125168. Epub 2025 Jan 3.

Abstract

The respiratory mucosa serves as a critical barrier against the invasion of pathogens. Effective mucosal vaccines are essential for enhancing local immunity. However, there is an urgent need to develop new mucosal adjuvants. Chitosan is preferred as a mucosal adjuvant due to its mucosal adhesion and immunostimulatory properties. In this work, a novel mucosal adjuvant was synthesized by combining nano-aluminum hydroxide and chitosan (Al-CS), formulating a particle size approximately 1.5 μm. In vitro assays revealed that Al-CS notably promotes antigen uptake by enhancing activation and maturation of dendritic cells and macrophages. Furthermore, in vivo experiments indicated that Al-CS could extend antigen release duration, facilitate immune cell migration to the lungs, stimulates antigen-presenting cell maturation, enhances antigen presentation and significantly improves both humoral and cellular immunity as well as B/T cell memory differentiation. The immunological potential of Al-CS exceeds that of either aluminum or chitosan alone, making it a promising and safe adjuvant for the advancement of mucosal vaccine carrier systems.

摘要

呼吸道黏膜是抵御病原体入侵的关键屏障。有效的黏膜疫苗对于增强局部免疫力至关重要。然而,迫切需要开发新型黏膜佐剂。壳聚糖因其黏膜黏附性和免疫刺激特性而被优选为黏膜佐剂。在本研究中,通过将纳米氢氧化铝和壳聚糖(Al-CS)结合,合成了一种新型黏膜佐剂,其粒径约为1.5μm。体外试验表明,Al-CS通过增强树突状细胞和巨噬细胞的活化与成熟,显著促进抗原摄取。此外,体内实验表明,Al-CS可延长抗原释放持续时间,促进免疫细胞向肺部迁移,刺激抗原呈递细胞成熟,增强抗原呈递,并显著改善体液免疫和细胞免疫以及B/T细胞记忆分化。Al-CS的免疫潜力超过单独的铝或壳聚糖,使其成为推进黏膜疫苗载体系统的一种有前景且安全的佐剂。

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