CORRELATES OF IMMUNE PROTECTION AGAINST TB IN BCG VACCINATED NONHUMAN PRIMATES

接种卡介苗的非人类灵长类动物中针对结核病的免疫保护的相关性

• 批准号: 8173025
• 负责人: Deepak Kaushal
• 金额: $ 3.94万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173025
• 关键词: Alveolar; Animal Experiments; Animals; Cells; Computer Retrieval of Information on Scientific Projects Database; Control Groups; Data; Data Analyses; Funding; Gene Expression; Gene Expression Profile; Genes; Grant; Granuloma; IL8 gene; Immune; Immune system; Infection; Infectious Diseases Research; Institutes; Institution; Interferon Type II; Interleukin-17; Interleukin-6; Irrigation; Louisiana; Lung; Macaca; Mycobacterium tuberculosis; Play; Research; Research Personnel; Resources; Role; Sampling; Seeds; Site; Source; Tuberculosis; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; cost; immune function; nonhuman primate; peripheral blood; pulmonary granuloma; vaccination against tuberculosis

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 最初，我们被资助以识别MTB感染后BCG接种猕猴的转录组（SPID 0941）。我们确定了一个小的离散基因基因，其表达因BCG疫苗接种而以统计学意义的方式受到干扰。免疫功能基因（例如Foxp3，MIP，IL-6和IL-24）在接种和对照组中均表达，以及IFN-GAMMA，IL-8，IL-8，IL-21，IL-17，IL-17，IL-27和RANTES，以及在BCG疫苗接种的动物肺中专门表达的。我们的结果清楚地表明，BCG疫苗接种可清楚有效地调节MTB感染部位的免疫系统。其中一些变化可能在诱导MTB感染的局部保护方面发挥作用。这些初步数据帮助我们通过路易斯安那州摄政委员会通过路易斯安那州疫苗疫苗中心（LVC）/南路易斯安那州传染病研究机制获得了合作种子资金（两年的每年75,000美元的总成本）。使用来自TNPRC试验的样品，我们研究了MTB感染后8个月的基因表达改变。 LVC基金将使我们能够将基因表达的短期变化（感染后1-3个月）随着MTB感染和BCG疫苗接种的函数而变化，这是肉芽肿的动力学演变。除了在肺淋巴瘤中的基因表达外，我们还将研究外周血中的基因表达和免疫细胞募集以及这些动物的支气管肺泡灌洗。动物实验最近已经完成。这些动物于2009年4月分配，于2009年5月通过BCG接种，并于2009年9月被MTB感染。所有动物均已安乐死并收集了样本。数据分析正在进行中。