Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism
Pulmonary but Not Subcutaneous Delivery of BCG Vaccine Confers Protection to Tuberculosis-Susceptible Mice by an Interleukin 17-Dependent Mechanism
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DOI：
10.1093/infdis/jiv503
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发表时间：
2016-03-01
影响因子：
6.4
通讯作者：
Martin, Carlos
中科院分区：
文献类型：
--
作者：
Aguilo, Nacho;Alvarez-Arguedas, Samuel;Martin, Carlos
目前正在开发的一些最有希望的新型结核病疫苗策略是基于呼吸道接种，模仿自然感染途径。在这项工作中，我们比较了肺和皮下接种卡介苗在结核易感DBA/2小鼠品系，一种模型，其中胃肠外接种卡介苗不能预防结核病。我们的数据表明，鼻内而非皮下接种卡介苗对肺结核的攻击具有强有力的保护作用。此外，我们的研究结果表明，肺疫苗接种引发结核分枝杆菌特异性粘膜免疫反应精心策划的白细胞介素17 A（IL-17 A）。因此，体内IL-17 A中和降低了保护作用并消除了M。肺结核特异性免疫球蛋白A（伊加）分泌到呼吸道和肺表达的多聚免疫球蛋白受体诱导后鼻内接种。总之，我们的研究结果表明，肺交付的卡介苗可以克服缺乏保护时观察到的卡介苗是胃肠外，这表明呼吸道结核疫苗可能有一个优势，在结核病流行的国家，皮内注射卡介苗对肺结核的有效性低。
Some of the most promising novel tuberculosis vaccine strategies currently under development are based on respiratory vaccination, mimicking the natural route of infection. In this work, we have compared pulmonary and subcutaneous delivery of BCG vaccine in the tuberculosis-susceptible DBA/2 mouse strain, a model in which parenterally administered BCG vaccine does not protect against tuberculosis. Our data show that intranasally but not subcutaneously administered BCG confers robust protection against pulmonary tuberculosis challenge. In addition, our results indicate that pulmonary vaccination triggers a Mycobacterium tuberculosis-specific mucosal immune response orchestrated by interleukin 17A (IL-17A). Thus, IL-17A neutralization in vivo reduces protection and abrogates M. tuberculosis-specific immunoglobulin A (IgA) secretion to respiratory airways and lung expression of polymeric immunoglobulin receptor induced following intranasal vaccination. Together, our results demonstrate that pulmonary delivery of BCG can overcome the lack of protection observed when BCG is given parenterally, suggesting that respiratory tuberculosis vaccines could have an advantage in tuberculosis-endemic countries, where intradermally administered BCG has inefficient effectiveness against pulmonary tuberculosis.