Protection against Mycobacterium leprae Infection by the ID83/GLA-SE and ID93/GLA-SE Vaccines Developed for Tuberculosis
Protection against Mycobacterium leprae Infection by the ID83/GLA-SE and ID93/GLA-SE Vaccines Developed for Tuberculosis
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DOI：
10.1128/iai.02145-14
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发表时间：
2014-09-01
影响因子：
3.1
通讯作者：
Reed, Steven G.
中科院分区：
文献类型：
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作者：
Duthie, Malcolm S.;Coler, Rhea N.;Reed, Steven G.
尽管20世纪90年代全世界麻风病例数量急剧减少，但病原体麻风分枝杆菌的传播仍在发生，并且不断出现新病例。消除麻风病需要新的战略。结核病疫苗开发中的交叉应用可能会产生适用于消除麻风病的工具。在本报告中，我们证明，作为结核病（TB）候选疫苗抗原而开发的嵌合融合蛋白ID83和ID93，可以从结核病和少杆菌（PB）麻风患者以及多杆菌（MB）患者（HHC）的健康家庭接触者中引起γ干扰素（IFN-γ）反应，但不会从未暴露的健康对照中引起反应。用含有 Toll 样受体 4 配体 (TLR4L) 的佐剂（稳定乳液中的吡喃葡萄糖脂佐剂 [GLA-SE]）配制的任一蛋白质对小鼠进行免疫，刺激多能 Th1 细胞分泌抗原特异性 IFN-γ。当免疫小鼠实验性感染麻风分枝杆菌时，与未免疫小鼠相比，局部淋巴结的细胞浸润和该部位的细菌生长均减少。因此，使用结核分枝杆菌候选疫苗 ID83/GLA-SE 和 ID93/GLA-SE 可能会产生针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用作麻风病的额外控制措施。
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-gamma) 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-gamma 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.