CORRELATES OF IMMUNE PROTECTION AGAINST TB IN BCG VACCINATED NONHUMAN PRIMATES

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目的总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 用致死剂量的高毒力Mtb Erdman株感染两组猕猴。在此之前17周，一组接种BCG，而另一组接种假疫苗。我们的研究结果表明，BCG显着和有效地保护NHP对挑战与致死剂量的结核分枝杆菌。相对于假疫苗接种的动物，BCG接种的动物存活，表现出更少的肺部病变和Mtb负荷，以及更低的炎症标志物表达。这些动物还在NHP的肺中表现出更强的CD 8特异性免疫应答。在假疫苗接种的动物中，我们观察到感染后1至2个月的转录重编程，与我们报告的通过气溶胶感染高剂量Mtb的恒河猴相似。这两组NHP之间的基因表达和细胞募集差异将使我们能够产生一个强大的多因子表达集，可用作人类TB感染进展和保护的未来生物标志物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Two groups of macaques were infected with a lethal dose of high-virulence Mtb Erdman strain. 17 weeks prior to this, one group had been vaccinated with BCG while another group had been sham-vaccinated. Our results indicate that BCG significantly and effectively protected NHPs against challenge with a lethal-dose of Mtb. Relative to sham-vaccinated animals, the BCG-vaccinated animals survived, exhibited fewer lung lesions and Mtb load, and lower expression of inflammatory markers. These animals also exhibited a more robust CD8-specific immune response in the lungs of NHPs. In sham-vaccinated animals, we observed a transcriptional reprogramming between 1 and 2 months after infection, similar to that reported by us for rhesus macaques infected with high-dose Mtb via aerosol. Gene-expression and cellular recruitment differences between these two groups of NHPs will allow us to generate a robust multi-factorial expression set that can be used as future biomarkers of progression of and protection from TB infections in humans.