CORRELATES OF IMMUNE PROTECTION AGAINST TB IN BCG VACCINATED NONHUMAN PRIMATES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们最初获得资助，以确定卡介苗接种猕猴感染结核分枝杆菌（SPID 0941）后的转录组。我们确定了一个小的，离散的一组基因的表达受到干扰，在统计学上显着的方式，作为卡介苗接种的结果。免疫功能基因如FoxP 3、MIP、IL-6和IL-24在接种组和对照组中均表达，而IFN-γ、IL-8、IL-21、IL-17、IL-27和RANTES仅在BCG接种动物肺中特异性表达。我们的研究结果清楚地表明，接种卡介苗明确和有效地调节结核分枝杆菌感染部位的免疫系统。这些变化中的一些可能在诱导局部保护免受结核分枝杆菌感染中起作用。这些初步数据帮助我们通过路易斯安那州疫苗中心（LVC）/南路易斯安那州传染病研究所机制，从路易斯安那州董事会获得合作种子资金（每年75，000美元，为期两年）。使用来自TNPRC试点的样本，我们观察了Mtb感染后8个月的基因表达变化。LVC基金将使我们能够观察作为结核分枝杆菌感染和卡介苗接种功能的基因表达的短期（感染后1-3个月）变化，以及肉芽肿的动态演变。除了在肺肉芽肿中的基因表达，我们还将研究这些动物外周血和支气管肺泡灌洗液中的基因表达和免疫细胞募集。动物实验已经完成。这些动物于2009年4月分配，2009年5月接种BCG，2009年9月感染Mtb。对所有动物实施安乐死并采集样本。数据分析正在进行中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We were initially funded to identify the transcriptome of BCG vaccinated macaques following infection with Mtb (SPID 0941). We identified a small, discrete group of genes whose expression was perturbed in a statistically significant manner, as a result of BCG vaccination. Immune function genes such as FoxP3, MIP, IL-6 and IL-24, which were expressed in both vaccinated and control groups, as well as IFN-gamma, IL-8, IL-21, IL-17, IL-27 and RANTES, which were specifically expressed, only in BCG vaccinated animal lungs. Our results clearly indicate that vaccination with BCG clearly and effectively modulates the immune system at the site of Mtb infection. Some of these changes may play a role in inducing localized protection from Mtb infection. These preliminary data helped us obtain cooperative seed funding ($75,000 per year total costs for a period of two years), from the Louisiana Board of Regents, through the Louisiana Vaccine Center (LVC)/South Louisiana Institute for Infectious Disease Research mechanism. Using samples from the TNPRC pilot, we looked at gene expression changes 8 months post Mtb infection. The LVC funds will allow us to look at short term (1-3 month post infection) changes in gene-expression as a function of Mtb infection and BCG vaccination, as the dynamics of the granuloma evolve. In addition to gene-expression in lung-granuloma's we will also study gene-expression and immune cell recruitment in peripheral blood and in Broncho-alveolar lavages of these animals. The animal experiment has recently been completed. These animals were assigned in Apr 2009, vaccinated with BCG in May 2009 and infected with Mtb in Sept 2009. All animals have been euthanized and samples collected. Data analysis is in progress.