Novel vaccine boosting candidates for tuberculosis

 描述（由申请人提供）：此R21非常简单。它解决了我们以前的证明，即新出现的结核病临床分离株，现在地球上最成功的细菌病原体，可以诱导调节性T细胞，这似乎直接干扰卡介苗接种引起的保护性免疫的表达。在这里，我们将确定是否“初免加强”BCG与两个非常有效的“减毒活突变体”提高免疫力和生存率超过BCG单独实现，以及这是否仍然发生在感染北京菌株的豚鼠中，该菌株有效诱导调节性T细胞。研究设计将包括BCG疫苗接种，然后加强，然后用两种高毒力临床分离株中的一种进行挑战，其中一种诱导调节性T细胞，另一种不诱导。我们将使用细菌学、免疫病理学、流式细胞术、RT-PCR和Kaplan-Meier分析来监测研究结局。

 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.