ABSTRACT

Tuberculosis (TB) is the most important infectious disease worldwide, based on the number of new cases and deaths reported by the World Health Organization. Several vaccine candidates against TB have been characterized at preclinical and clinical levels. The BCGΔBCG1419c vaccine candidate, which lacks the BCG1419c gene that encodes for a c-di-GMP phosphodiesterase, provides improved efficacy against chronic TB, reactivation from latent-like infection and against chronic TB in the presence of type 2 diabetes in murine models. We previously reported that compared with wild type BCG, BCGΔBCG1419c changed levels of several proteins. Here, using a label-free proteomic approach, we confirmed that a novel, second-generation version of BCGΔBCG1419c maintains changes in antigenic proteins already reported, and here we further found differences in secreted proteins, as well as that this new BCGΔBCG1419c version modifies its production of proteins involved in redox and nitrogen/protein metabolism compared with wild type BCG. This work contributes to the proteomic characterization of a novel vaccine candidate that is more effective against TB than parental BCG in diverse murine models.

中文翻译：

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通过电喷雾电离四极杆飞行时间质谱法对第二代 BCGΔBCG1419c 候选疫苗进行蛋白质组学表征

摘要

根据世界卫生组织报告的新病例和死亡人数，结核病 (TB) 是全球最重要的传染病。已经在临床前和临床水平表征了几种抗结核疫苗候选物。缺少BCG1419c的 BCGΔBCG1419c 候选疫苗编码 c-di-GMP 磷酸二酯酶的基因，在小鼠模型中提供了对慢性 TB、潜伏样感染的再激活和在存在 2 型糖尿病的情况下对慢性 TB 的改进功效。我们之前报道过，与野生型 BCG 相比，BCGΔBCG1419c 改变了几种蛋白质的水平。在这里，使用无标记蛋白质组学方法，我们证实了 BCGΔBCG1419c 的第二代新版本保持了已经报道的抗原蛋白的变化，在这里我们进一步发现了分泌蛋白的差异，以及这个新的 BCGΔBCG1419c 版本修改了其与野生型 BCG 相比，参与氧化还原和氮/蛋白质代谢的蛋白质的产生。