基于新型金属-有机骨架材料的中国人群优势MHC限制性结核分枝杆菌Th1表位疫苗Ag85AB-CMPRT的免疫保护性及机制研究

结核病是一种全球性传染病，但缺乏有效的疫苗。研究表明能否诱导CD4+T细胞产生高水平IFN-γ是抗结核感染的关键。本课题组前期研究发现了9个全新的中国人群优势MHC限制性结核分枝杆菌Th1表位，它们能够刺激中国人群优势HLA-A11/DR1转基因C57BL/6小鼠CD4+T细胞增殖并分泌高水平的IFN-γ。我们将上述表位与Ag85AB抗原线性串联后构建了Th1表位疫苗Ag85AB-CMPRT，并首次将金属-有机骨架材料（MOFs）应用于结核疫苗的递呈。本项目拟以Ag85AB-CMPRT@MOFs为研究对象分别免疫HLA-A11/DR1转基因C57BL/6小鼠和野生型C57BL/6小鼠，观察其免疫原性、病理特征及免疫保护性，并且从动物、细胞和分子水平初步阐述其免疫保护机制。本研究将为中国人群优势MHC限制性结核Th1表位疫苗的研发提供新靶标，也将为结核的预防治疗提供新思路。

Tuberculosis (TB) is a serious infectious disease, but it lacks effective vaccines. The current studies showed that the ability to induce CD4+ T cells to produce high levels of IFN-γ is the key to anti-TB. Our previous studies have identified 9 novel Chinese dominant MHC restricted epitope peptides of Mycobacterium tuberculosis (MTB) which could stimulate CD4+T cells collected form MTB-immunized HLA-A11/DR1 humanized C57BL/6 mouse proliferating and secreting high levels of IFN-γ. After optimizing these epitope peptides with Ag85AB antigen, we constructed a new TB vaccine termed Ag85AB-CMPRT and further assembled it with the metal-organic frameworks (MOFs). In this study, the immunogenicity, pathological features and immunoprotection of Ag85AB-CMPRT@MOFs will be determined on HLA-A11/DR1 humanized C57BL/6 mice and wild-type C57BL/6 mice, respectively. Furthermore, a series of methods will be performed to explore the immune protection mechanism of Ag85AB-CMPRT@MOFs. The results might provide new targets for the design of MTB Th1 epitope vaccine, and give a new perspective for prevention and treatment of TB.