BCG efficacy against W-Beijing TB strains

描述(申请人提供)：我们有越来越多的证据表明，卡介苗的保护作用在从美国患者中分离的结核分枝杆菌[主要是北京家庭]菌株与在南非西开普省收集的菌株之间存在很大差异，西开普省是目前结核病疫苗试验的地点。我们已经证明，卡介苗对美国北京病毒株只有短暂的保护作用，但对两种西开普省病毒株在豚鼠身上具有高度保护作用。因此，R21应用的目的是测试卡介苗对两种更大的 [b]以检验有能力抵抗卡介苗保护作用的菌株之所以能够抵抗卡介苗的保护作用，是因为它们能够有效地诱导抑制这种免疫的调节性T细胞，这一假说基于我们实验室提供的大量新证据。这些研究不仅对公共卫生有重大影响，特别是对新的疫苗试验，而且如果西开普省的毒株像我们的初步数据所显示的那样对卡介苗敏感，它们为最近的MVA85A试验失败提供了解释。这些研究将在CSU最先进的III级设施中进行，使用我们擅长的传统技术。

DESCRIPTION (provided by applicant): We have increasing evidence that the protective effect of BCG varies widely between strains of M. tuberculosis [mostly of the Beijing family] isolated from patients in the USA, and those collected in the Western Cape of South Africa, the site of current TB vaccine trials. We have shown that BCG is only transiently protective against the US Beijing strains, but highly protective against two Western Cape strains in guinea pigs. The purpose of this R21 application therefore is to test [a] the efficacy of BCG against two larger panels representative of the two groups of isolates to see if our preliminary data is a collective phenomenon, and [b] to test the hypothesis that strains that have the capacity to resist the protective effects of BCG are able to do so because they potently induce regulatory T cells that inhibit this immunity, a hypothesis based on considerable new evidence from our laboratory. Not only do these studies have significant public health implications, notably for new vaccine trials, but if the Western Cape strains are as sensitive to BCG as our preliminary data suggests, they provide an explanation for the failure of the recent MVA85A trial. These studies will be conducted in our state of the art level-III facilities at CSU using conventional techniques at whic we are adept.