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Protection against Mycobacterium leprae Infection by the ID83/GLA-SE and ID93/GLA-SE Vaccines Developed for Tuberculosis

机译:针对肺结核开发的ID83 / GLA-SE和ID93 / GLA-SE疫苗对麻风分枝杆菌感染的保护

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摘要

Despite the dramatic reduction in the number of leprosy cases worldwide in the 1990s, transmission of the causative agent, Mycobacterium leprae, is still occurring, and new cases continue to appear. New strategies are required in the pursuit of leprosy elimination. The cross-application of vaccines in development for tuberculosis may lead to tools applicable to elimination of leprosy. In this report, we demonstrate that the chimeric fusion proteins ID83 and ID93, developed as antigens for tuberculosis (TB) vaccine candidates, elicited gamma interferon (IFN-γ) responses from both TB and paucibacillary (PB) leprosy patients and from healthy household contacts of multibacillary (MB) patients (HHC) but not from nonexposed healthy controls. Immunization of mice with either protein formulated with a Toll-like receptor 4 ligand (TLR4L)-containing adjuvant (glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) stimulated antigen-specific IFN-γ secretion from pluripotent Th1 cells. When immunized mice were experimentally infected with M. leprae, both cellular infiltration into the local lymph node and bacterial growth at the site were reduced relative to those of unimmunized mice. Thus, the use of the Mycobacterium tuberculosis candidate vaccines ID83/GLA-SE and ID93/GLA-SE may confer cross-protection against M. leprae infection. Our data suggest these vaccines could potentially be used as an additional control measure for leprosy.
机译:尽管1990年代全世界麻风病病例数急剧减少,但致病因子麻风分枝杆菌仍在传播,新病例继续出现。追求消除麻风病需要新的策略。疫苗在结核病研发中的交叉应用可能会导致可用于消除麻风的工具。在本报告中,我们证明了嵌合融合蛋白ID83和ID93作为结核病(TB)候选疫苗的抗原开发,引起了结核病和结核性麻风(PB)麻风患者以及健康家庭接触者的γ干扰素(IFN-γ)反应多细菌(MB)患者(HHC),但不是来自未暴露的健康对照者。用包含Toll样受体4配体(TLR4L)的佐剂(稳定乳剂中的吡喃葡萄糖基脂质佐剂)配制的蛋白质对小鼠进行免疫,可刺激多能Th1细胞分泌抗原特异性IFN-γ。当对免疫小鼠进行麻风分枝杆菌实验感染时,相对于未免疫小鼠而言,进入局部淋巴结的细胞浸润和该部位的细菌生长都减少了。因此,结核分枝杆菌候选疫苗ID83 / GLA-SE和ID93 / GLA-SE的使用可以赋予对麻风分枝杆菌感染的交叉保护。我们的数据表明,这些疫苗有可能被用作麻风的其他控制措施。

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