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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 两组猕猴被感染了致命剂量的高毒力Mtb Erdman菌株。在此之前17周，一组接种了卡介苗，另一组接种了假疫苗。我们的结果表明，卡介苗显著而有效地保护NHP免受致死剂量的Mtb的攻击。与假疫苗接种的动物相比，接种卡介苗的动物存活了下来，表现出较少的肺部病变和结核分枝杆菌载量，以及较低的炎症标志物表达。这些动物在NHP的肺中也表现出更强大的CD8特异性免疫反应。在假疫苗接种的动物中，我们在感染后1-2个月观察到转录重编程，类似于我们报道的通过气雾剂感染高剂量结核分枝杆菌的恒河猴。这两组NHP之间的基因表达和细胞招募差异将使我们能够产生一个强大的多因素表达集，可用作未来人类结核病感染进展和保护的生物标记物。

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.