BCG efficacy against W-Beijing TB strains

卡介苗对W-北京结核菌株的功效

• 批准号: 8681113
• 负责人: IAN M ORME
• 金额: $ 18.59万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-07 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681113
• 关键词: Adoptive Transfer; Animal Model; Area; Asia; Cavia; Cell Separation; Cells; Clinical; Data; Disease Outbreaks; Drug resistance; Event; Failure; Family; Fingers; Gold; Immunity; Incidence; Infant; Knock-in Mouse; Laboratories; Learning; Lung; Modeling; Mus; Mycobacterium tuberculosis; Paper; Pathology; Patients; Planets; Public Health; Reading; Regulatory T-Lymphocyte; Resistance; San Francisco; Shame; Site; South Africa; Speed; Study Section; T-Lymphocyte; Techniques; Testing; Tuberculosis; Tuberculosis Vaccines; Vaccines; Virulence; Virulent; Visit; Work; arm; base; cost; mRNA Expression; novel vaccines; programs; protective effect; public health relevance; resistant strain; vaccination against tuberculosis; vaccine evaluation

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.

描述（由申请人提供）：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分离出的结核分枝杆菌菌株（主要是北京家族）和在南非西开普省收集的结核分枝杆菌菌株之间存在很大差异，目前结核病疫苗试验的地点。我们已经证明，卡介苗仅对美国北京菌株具有短暂的保护作用，但对豚鼠中的两种西开普菌株具有高度保护作用。因此，该 R21 申请的目的是测试 [a] BCG 针对两种较大的药物的功效 代表两组分离株的小组，看看我们的初步数据是否是一个集体现象，并[b]检验以下假设：有能力抵抗卡介苗保护作用的菌株之所以能够这样做，是因为它们有效地诱导了监管T 细胞抑制这种免疫，这一假设基于我们实验室的大量新证据。这些研究不仅对公共卫生具有重大影响，特别是对于新疫苗试验，而且如果西开普毒株如我们的初步数据所显示的那样对卡介苗敏感，它们就为最近 MVA85A 试验的失败提供了解释。这些研究将在科罗拉多州立大学最先进的三级设施中使用我们擅长的传统技术进行。