Mycobacteria interactions and vaccine efficacy

分枝杆菌相互作用和疫苗功效

• 批准号: 6604467
• 负责人: JOANNE TURNER
• 金额: $ 22.43万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604467
• 关键词: Bacillus Calmette Guerin vaccine; Mycobacterium; Mycobacterium tuberculosis; active immunization; bacterial antigens; cross immunity; environmental exposure; laboratory mouse; leukocyte activation /transformation; microorganism interaction

DESCRIPTION (provided by applicant): Exposure to "atypical" or "environmental" mycobacteria [EM] is believed to be the primary mechanism thought to be responsible for the reduced efficacy of the BCG vaccine against tuberculosis in many parts of the world. To date however, the exact mechanism by which EM interfere with the development of protective immunity in response to vaccination still remains unknown. It has been hypothesized that constant exposure to cross-reactive antigens can sequester specific cells at alternative sites in the body, or that the immune response generated against environmental mycobacteria is strong enough to control BCG before its protective effect can be acquired. The studies documented in the literature however have used several different exposure protocols making interpretation of the results very difficult. This application seeks to carry out an analytical study using standardized exposure protocols. We propose to administer environmental mycobacteria either before BCG vaccination (to determine whether environmental exposure interferes with the generation of immunity against the vaccine) or following BCG vaccination (to determine whether environmental exposure influences the long-term efficacy of BCG). Throughout the study we will isolate immune cells from the draining lymph nodes and lungs and determine whether cells become sequestered at the site of environmental exposure, become highly activated in response to mycobacterial antigens, or become deleted from the lymphocyte pool. Using these methods we aim to determine the basis of the microbial interactions between EM and BCG that underlies the failure of the vaccine to protect against infection with M. tuberculosis. In addition, we propose to carry out a preliminary proteomics study to identify key antigens from M. tuberculosis that are absent from EM that could be incorporated into a sub-unit vaccine.

描述(由申请人提供)：在世界许多地区，接触“非典型”或“环境”分枝杆菌[EM]被认为是导致卡介苗抗结核效果降低的主要机制。然而，到目前为止，EM干扰保护性免疫发展以应对疫苗接种的确切机制仍不清楚。有人假设，持续接触交叉反应抗原可以将特定细胞隔离在体内不同的位置，或者对环境分枝杆菌产生的免疫反应足够强大，足以在获得卡介苗的保护作用之前控制它。然而，文献中记载的研究使用了几种不同的暴露方案，使得对结果的解释非常困难。本申请寻求使用标准化暴露方案进行分析研究。我们建议在接种卡介苗之前(确定环境暴露是否干扰对疫苗免疫的产生)或在接种卡介苗之后(确定环境暴露是否影响卡介苗的长期疗效)接种环境分枝杆菌。在整个研究过程中，我们将从引流的淋巴结和肺中分离免疫细胞，并确定细胞是否在环境暴露部位隔离，对分枝杆菌抗原高度激活，或从淋巴细胞池中删除。使用这些方法，我们的目标是确定EM和卡介苗之间微生物相互作用的基础，这是疫苗未能预防结核分枝杆菌感染的基础。此外，我们建议开展一项初步的蛋白质组学研究，以确定EM中不存在的结核分枝杆菌关键抗原，这些抗原可以被整合到亚单位疫苗中。