表达HBHA和hIL-12融合蛋白的重组耻垢分枝杆菌在小鼠体内诱导的免疫应答及保护力

Immune Responses and Protection Induced by a Recombinant Mycobacterium smegmatis Expressing an HBHA and hIL-12 Fusion Protein Against M.tuberculosis Infection

目的:测定表达肝素结合血凝素(HBHA)和人白细胞介素12(hIL-12)融合蛋白的重组耻垢分枝杆菌在小鼠体内诱导产生的免疫应答及对结核分枝杆菌感染的保护作用。方法:将表达HBHA和hIL-12融合蛋白的重组耻垢分枝杆菌采用同源加强免疫的方法免疫小鼠,检测小鼠外周血中IFN-γ、IL-2和IL-12的表达水平;用结核分枝杆菌感染免疫小鼠,检测小鼠肺部荷菌量和组织病理变化。结果:表达HBHA和hIL-12融合蛋白的重组耻垢分枝杆菌诱导小鼠产生以IFN-γ、IL-2分泌量增加为主的Th1型免疫应答,并能有效减少感染小鼠肺部结核分枝杆菌的荷菌量和病理损伤。结论:表达HBHA和hIL-12融合蛋白的重组耻垢分枝杆菌免疫小鼠可诱导产生与卡介苗相当的保护作用,可能成为控制结核病的有效疫苗。

Objective： The immune responses induced by the recombinant Mycobacterium smegmatis that expressing heparin-binding haemagglutinin（HBHA） and the human interleukin 12（hIL-12） in the mice and protection against M.tuberculosis were investigated. Methods： The groups of mice were vaccinated by the homologous prime-boost method. A number of mice in each group were used for analysis of lymphocyte proliferation index, IFN-γ IL-2, IL-12. The other mice in each group were retained for an M. tuberculosis virulent strain H37Rv infec tion experiment. Results： Administration of this novel recombinant M.smegmatis enhanced Thl-type cellular responses in mice by producing higher amounts of IFN-γ and IL-2, and reduce bacterial burden in lungs. Conclusion： The protection effect induced by the recombinant M.smegmatis reached the equivalent level as conventional BCG in mice. The recombinant M.smegmatis can be considered as a TB vaccine candidate in TB vaccines.