"Genetic Approaches for Improving Tuberculosis Vaccines"

需要一种有效和安全的结核病疫苗。这个项目的目标是开发一种新的结核病 疫苗候选株M.结核和M.恶臭安全是通过生成 在免疫缺陷小鼠中不能生长的减毒突变体。为了产生更有效的结核病 疫苗，该项目将产生具有增强免疫原性的突变体。增强的免疫原性 可以通过识别突变来实现，这些突变可以抑制逃避宿主先天和适应性的决定因素， 免疫反应。M.结核病具有主动抑制THI细胞因子的诱导的能力。目的 1利用了使用含有编码绿色荧光蛋白的基因的巨噬细胞系的筛选， 融合至IL-12诱导型启动子的蛋白。转座子和无效缺失突变体减毒M。 将针对诱导IL-12的能力筛选肺结核。M.结核病积极阻止细胞凋亡。 目的2使用遗传筛选来鉴定凋亡阻断效应子（abe）突变。分离出的突变体 将评价Aim 1和Aim 2在保护小鼠免受雾化M的影响方面的功效。 结核病挑战使用M.结核病H37 Rv和来自南非的KZN菌株。初步 Aim 3的数据已经在M.斯米加因天生的杀戮逃避而命名为艾克。的 M.用M. smegalyptus Aike突变体含有一组M. 结核分枝杆菌基因（IKEPLUS）能产生抗结核分枝杆菌的杀菌免疫。结核 异源初免和ILEPLUS和减毒M加强。结核病将被研究。 相关性（见说明）：

An efficacious and safe vaccine is needed for Tuberculosis. The goal of this project is to develop a novel TB vaccine candidate strains of M. tuberculosis and M. smegmatis. Safety is achieved by generating attenuated mutants that fail to grow in immunocompromised mice. To generate a more efficacious TB vaccine, this project will generate mutants that have enhanced immunogenicity. Enhanced immunogenicity can be achieved by identifying mutations that inactivate determinants that evade host innate and adaptive immune responses. M. tuberculosis has the ability to actively suppress the induction of THI cytokines. Aim 1 utilizes a screen employing a macrophage cell line containing the gene encoding the green fluorescent protein fused to the IL-12 inducible promoter. Transposon and null deletion mutants of attenuated M. tuberculosis will be screened for the ability to induce IL-12. M. tuberculosis actively prevents apoptosis. Aim 2 uses a genetic screen to identify apoptotic blocking effectors (abe) mutations. The mutants isolated in both Aim 1 and Aim 2 will be evaluated for their efficacy in protecting mice against aerosolized M. tuberculosis challenges using both M. tuberculosis H37Rv and the KZN strain from South Africa. Preliminary data for Aim 3 has identified a novel set of genes in M. smegmatis named ike for innate killing evasion. The M. smegmatis Aike deletion Mice immunized with M. smegmatis Aike mutant containing a set of M. tuberculosis genes (named IKEPLUS) elicits a bactericidal immunity against M. tuberculosis. Heterologous prime and boosts with ILEPLUS and attenuated M. tuberculosis will be explored. RELEVANCE (See instmctions):