中文摘要：研究构建了2个不同的纳米抗原传递系统，一个为包含可溶性抗原核的胶囊化多聚体（PSs），一个是表面点缀抗原的纳米颗粒（NPs）；试验表明，PSs更有利于增强CD4 T细胞和抗体滴度，而NPs有利于增强细胞毒素CD8 T细胞反应。研究证实，不同的T细胞反应反映出淋巴组织中不同的胞内激活模式和可溶性抗原的分布，这些都是由各种纳米传递系统的特性决定的。包含可溶性抗原的PSs更能促进CD4 T细胞激活，诱导产生更多的CD4 T细胞滤泡辅助细胞。这些差异与生发中心B细胞和血浆细胞的浓度改变相关，从而反应在抗体滴度的变化上。这些研究结果表明，PSs 是B细胞特异性疫苗可溶性抗原的理想传递载体。
外文摘要：Nanoparticle delivery systems are known to enhance the immune response to soluble antigens (Ags) and are thus a promising tool for the development of new vaccines. Our laboratory has engineered two different nanoparticulate systems in which Ag is either encapsulated within the core of polymersomes (PSs) or decorated onto the surface of nanoparticles (NPs). Previous studies showed that PSs are better at enhancing CD4 T cells and antibody titers, while NPs preferentially augment cytotoxic CD8 T cells. Herein, we demonstrate that the differential activation of T cell immunity reflects differences in the modes of intracellular trafficking and distinct biodistribution of the Ag in lymphoid organs, which are both driven by the properties of each nanocarrier. Furthermore, we found that Ags within PSs promoted better CD4 T cell activation and induced a higher frequency of CD4 T follicular helper (Tfh) cells. These differences correlated with changes in the frequency of germinal center B cells and plasma cell formation, which reflects the previously observed antibody titers. Our results show that PSs are a promising vector for the delivery of Ags for B cell vaccine development. This study demonstrates that nanocarrier design has a large impact on the quality of the induced adaptive immune response.
外文关键词：Vaccine design; Antigen presentation; T follicular helper cells; Germinal center; Dendritic cells
作者：Rincon-Restrepo, M; Mayer, A; Hauert, S; Bonner, DK; Phelps, EA; Hubbell, JA; Swartz, MA; Hirosue, S
作者单位：瑞典洛桑联合理工大学
期刊名称：BIOMATERIALS
期刊影响因子：8.387
出版年份：2017
出版刊次：7
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