中文摘要：研究研制了一种新型粘膜结核分歧杆菌疫苗（Nano-FP1），该疫苗基于黄色巴西蜡棕蜡纳米颗粒（YC-NPs）构建，表面采用融合蛋白包裹，该融合蛋白包含3种结核分歧杆菌（Mtb）抗原Acr、 Ag85B和HBHA。采用Nano-FP1粘膜免疫BCG感染小鼠能够显著增强小鼠对低剂量、雾化结核分歧杆菌的保护作用；Nano-FP1的抗菌能力与细胞性免疫作用增强相关，包括CD4(+)和CD8(+)的优先增殖，肺部组织常驻记忆T细胞（Trm）繁殖和细胞因子的多功能化。除了这些作用外，研究也观察到了潜在的体液反应，包括Ag85B-特异性血清IgG和呼吸性IgA的产生。研究最后发现，YC-NPs能够通过一种非常规的IRF-3-相关的激活方式激活抗原呈递细胞，而不会产生有害的炎症性调节因子，本研究为提高疫苗效率、开发新疫苗提供了重要框架。
外文摘要：Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Cahnette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA. Mucosal immunization of BCG-primed mice with Nano-FP1 significantly enhanced protection in animals challenged with low dose, aerosolized Mtb. Bacterial control by Nano-FP1 was associated with dramatically enhanced cellular immunity compared to BCG, including superior CD4(+) and CD8(+) T cell proliferation, tissue-resident memory T cell (Trm) seeding in the lungs, and cytokine polyfunctionality. Alongside these effects, we also observed potent humoral responses, such as the generation of Ag85B-specific serum IgG and respiratory IgA. Finally, we found that YC-NPs were able to activate antigen-presenting cells via an unconventional IRF-3-associated activation signature, without the production of potentially harmful inflammatory mediators, providing a mechanistic framework for vaccine efficacy and future development.
 
外文关键词： DENDRITIC CELL MATURATION; MONOPHOSPHORYL-LIPID-A; CD4 T-CELLS; VACCINE ADJUVANT; IMMUNITY; EXPRESSION; MEMORY; TRIF; BCG; MACROPHAGES
作者：Hart, P; Copland, A; Diogo, GR; Harris, S; Spallek, R; Oehlmann, W; Singh, M; Basile, J; Rottenberg, M; Paul, MJ; Reljic, R
作者单位：英国伦敦大学
期刊名称：MOLECULAR THERAPY
期刊影响因子：5.6
出版年份：2018
出版刊次：3
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