中文摘要：本研究表明，可以用融合蛋白1（FP1）包被枯草芽孢杆菌，该融合蛋白1由结核分歧杆菌（Mtb）抗原Ag85B、ACR和HBHA组成，组装后的疫苗命名为Spore-FP1。采用小鼠低剂量结核杆菌喷雾感染模型检测该疫苗的免疫原性和保护作用。结果表明，Spore-FP1能够增强肺部对结核杆菌感染的控制作用，这一点可以通过肺部细菌负载量证明；随着肺部感染结核杆菌控制作用的增强，小鼠血浆和肺表明抗原特异性IgG和IgA滴度增加。与单独使用卡介苗免疫相比，采用Spore-FP1免疫能够优先促进CD4(+)和CD8(+)中抗原特异性记忆T细胞增殖，提高Th1-、Th17-及调节性T细胞因子水平。粘膜免疫Spore-FP1后，肺实质部位CD69(+) CD103(+)组织中发现记忆T细胞（Trm），这也验证了粘膜传递的优势。本研究结果表明，Spore-FP1可以为结核感染动物提供免疫保护作用，作为一种新型结核病疫苗前景广阔。
 
外文摘要：Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guerin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model. Mice were primed with subcutaneous BCG, followed by mucosal booster immunizations with Spore-FP1. We show that Spore-FP1 enhanced pulmonary control of Mtb, as evidenced by reduced bacterial burdens in the lungs. This was associated with elevated antigen-specific IgG and IgA titers in the serum and lung mucosal surface, respectively. Spore-FP1 immunization generated superior antigen-specific memory T-cell proliferation in both CD4(+) and CD8(+) compartments, alongside bolstered Th1-, Th17-, and Tregtype cytokine production, compared to BCG immunization alone. CD69(+) CD103(+) tissue resident memory T-cells (Trm) were found within the lung parenchyma after mucosal immunization with Spore-FP1, confirming the advantages of mucosal delivery. Our data show that Spore-FP1 is a promising new TB vaccine that can successfully augment protection and immunogenicity in BCG-primed animals.
 
外文关键词：tuberculosis, spores, vaccine, immunity, adjuvants
作者： Copland, A; Diogo, GR; Hart, P; Harris, S; Tran, AC; Paul, MJ; Singh, M; Cutting, SM; Reljic, R
作者单位：英国伦敦圣乔治医学院
期刊名称： FRONTIERS IN IMMUNOLOGY
期刊影响因子：6.43
出版年份：2018
出版刊次：3
点击下载：粘膜传递携带枯草芽孢杆菌的融合蛋白可以增强卡介苗抗肺结核的保护作用