Novel vaccine boosting candidates for tuberculosis

 描述(申请人提供)：这款R21非常简单。它解决了我们之前的演示，即新出现的结核病临床分离株，现在是地球上最成功的细菌病原体，可以诱导调节性T细胞，似乎直接干扰BCG疫苗诱导的保护性免疫的表达。在这里，我们将确定用两个非常有效的“活的减毒突变株”来“主要增强”卡介苗是否比单独使用卡介苗能提高免疫力和存活率，以及这种情况是否仍然发生在感染了北京菌株的豚鼠身上，这种菌株可以有效地诱导调节性T细胞。研究设计将包括接种卡介苗，然后加强免疫，然后挑战两个高毒力临床分离株中的一个，其中一个诱导调节性T细胞，另一个不诱导。我们将使用细菌学、免疫病理学、流式细胞术、RT-PCR和Kaplan-Meier分析来监测研究结果。

 DESCRIPTION (provided by applicant): This R21 is very simple. It addresses our previous demonstrations that newly emerging clinical isolates of tuberculosis, now the most successful bacterial pathogen on the planet, can induce regulatory T cells which seem to directly interfere with the expression of protective immunity elicited by vaccination with BCG. Here, we will determine if "prime boosting" BCG with two very potent "live attenuated mutants" improve immunity and survival beyond that achieved by BCG alone, and whether this still happens in guinea pigs infected with a Beijing strain that potently induces regulatory T cells. The research design will consist of BCG vaccination followed by boosting and then challenge with one of two highly virulent clinical isolates, one of which induces regulatory T cells and one that does not. We will use bacteriology, immunopathology, flow cytometry, RT-PCR, and Kaplan-Meier analysis to monitor study outcomes.