BCG efficacy against W-Beijing TB strains

卡介苗对W-北京结核菌株的功效

• 批准号: 8803276
• 负责人: IAN M ORME
• 金额: $ 22.31万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803276
• 关键词: Adoptive Transfer; Animal Model; Area; Asia; Cavia; Cell Separation; Cells; Clinical; Data; Disease Outbreaks; Drug resistance; Event; Failure; Family; Fingers; Gold; Health; 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; resistant strain; vaccination against tuberculosis; vaccine evaluation; vaccine trial

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不同的分枝杆菌菌株之间有很大的差异。从美国患者中分离出的结核病[主要是北京家族]，以及在南非西开普省收集的结核病疫苗，目前的结核病疫苗试验地点。我们已经证明，BCG对美国北京菌株只有短暂的保护作用，但对豚鼠中的两种西开普菌株具有高度保护作用。因此，这项R21申请的目的是测试[a]卡介苗对两种较大的 这两组分离株的代表小组，看看我们的初步数据是否是一个集体现象，[B]以检验假设，即有能力抵抗BCG保护作用的菌株能够这样做，因为它们有效地诱导抑制这种免疫力的调节性T细胞，这一假设基于我们实验室的大量新证据。这些研究不仅具有重大的公共卫生意义，特别是对于新疫苗试验，而且如果西开普省菌株像我们的初步数据显示的那样对BCG敏感，它们为最近的MVA 85 A试验失败提供了解释。这些研究将在CSU最先进的三级设施中使用我们擅长的传统技术进行。

项目成果

The Efficacy of the BCG Vaccine against Newly Emerging Clinical Strains of Mycobacterium tuberculosis.

• DOI: 10.1371/journal.pone.0136500
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Henao-Tamayo M;Shanley CA;Verma D;Zilavy A;Stapleton MC;Furney SK;Podell B;Orme IM
• 通讯作者: Orme IM