基于减毒假结核耶尔森菌T3SS递送系统的金黄色葡萄球菌疫苗设计及免疫保护效果研究

金黄色葡萄球菌乳腺炎是危害畜牧业发展的重大疾病之一。国内外针对金黄色葡萄球菌疫苗研究做了大量探索，但均未取得满意效果。究其原因，主要与这些疫苗未能引起足够的细胞免疫应答有关。已有研究表明，利用细菌III 型分泌系统(T3SS)，可以直接将异源抗原递呈到免疫细胞内，在诱导抗原特异性细胞免疫应答上具有独特优势。项目组前期研究发现，减毒假结核耶尔森菌作为载体递送金黄色葡萄球菌抗原，对于抵抗金黄色葡萄球菌感染具有良好效果。本项目拟在前期研究基础上，进一步改造假结核耶尔森菌，构建减毒假结核耶尔森菌T3SS 递送金黄色葡萄球菌抗原表达系统，研制新型金黄色葡萄球菌疫苗；通过小鼠和奶山羊乳腺炎模型，系统评价疫苗的免疫保护效果和免疫应答特征。研究结果将为金黄色葡萄球菌乳房炎疫苗研制提供新的思路和实验依据。

Staphylococcus aureus mastitis is one of the most serious diseases that threaten the dairy farm.Researchers around the world have done a lot of work on the development of S. aureus vaccine, but there is still no effective vaccine in clinical practice. In the previous researches, different types of vaccines haven’t shown as good results as expected. It’s most likely that these vaccines can’t induce sufficient cellular immune response. Previous studies have shown that type 3 secretion system (T3SS) in bacteria can directly deliver heteroantigens into immune cells, which has a unique advantage in inducing antigen-specific cellular immune response. Meanwhile, our study has shown that, as S. aureus protective antigen delivery vector, recombinant attenuated Yersinia pseudotuberculosis (Yptb) does well in resisting S. aureus infection. The objective of this study is design and to characterize the protective efficacy of staphylococcus aureus antigens delivered via live attenuated Yptb T3SS effector proteins. Specifically, we propose to construct novel live attenuated Yptb strains and delivered S. aureus antigens via T3SS. Furthermore, we will evaluate the protective efficacy and characterize of immune response of this novel S. aureus mucosal vaccine in murine and dairy goats model of staphylococcal mastitis. These studies will represent essential steps toward the development of novel S. aureus vaccine.