State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health & School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, 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 Sciences, Xiamen University, Xiamen, Fujian 361102, 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.
J Control Release. 2024 Jan;365:369-383. doi: 10.1016/j.jconrel.2023.11.025. Epub 2023 Nov 30.
Micro/Nano-scale particles are widely used as vaccine adjuvants to enhance immune response and improve antigen stability. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti-osteoporotic drug, to create zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, micronanoparticled Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in lymph nodes, and facilitated the rapid production of antibodies. Importantly, Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 challenge. Consequently, particulate risedronate showed great potential as an immune-enhancing vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.
微/纳米颗粒被广泛用作疫苗佐剂,以增强免疫反应和提高抗原稳定性。虽然铝盐是最常用于人体的佐剂之一,但它的免疫刺激能力并不理想。在这项研究中,我们修饰了利塞膦酸盐(一种免疫刺激剂和抗骨质疏松药物),创建了基于锌盐颗粒的利塞膦酸盐(Zn-RS),也称为颗粒状利塞膦酸盐。与可溶性利塞膦酸盐相比,微米纳米颗粒 Zn-RS 佐剂表现出更多的固有细胞募集,增强了局部抗原摄取,并具有与铝盐相似的抗原储存效应。此外,Zn-RS 佐剂直接且快速地刺激免疫细胞,加速淋巴结中生发中心的形成,并促进抗体的快速产生。重要的是,Zn-RS 佐剂在年轻和老年小鼠中均表现出优异的性能,有效预防了 SARS-CoV-2 等呼吸道疾病的挑战。因此,颗粒状利塞膦酸盐作为一种增强免疫的疫苗佐剂具有巨大的潜力,特别有益于针对易感老年人的疫苗。
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