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首页> 外文期刊>Vaccines >Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice
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Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice

机译：结核分枝杆菌亚单位疫苗的预防性舌下免疫与天然杀伤性T细胞激动剂α-半乳糖苷神经酰胺的结合增强了保护性免疫力，从而限制了小鼠的肺和肺外细菌负担

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Infection by Mycobacterium tuberculosis (Mtb) remains a major global concern and the available Bacillus Calmette-Guerin (BCG) vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (???±-GalCer), a potent natural killer T (NKT) cell agonist. Vaccinated animals exhibited strong antigen-specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and lungs. In general, inclusion of the ???±-GalCer adjuvant significantly enhanced these responses that persisted over 50 days. Furthermore, aerosolized Mtb infection of vaccinated mice resulted in a significant reduction of bacterial load of the lungs and spleens as compared to levels seen in na???ˉve controls or those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection induced by the Mtb antigens and-GalCer vaccine through sublingual route correlated with a TH1-type immunity mediated by antigen-specific IFN-???3 and IL-2 producing T cells.
机译：结核分枝杆菌（Mtb）感染仍然是全球主要关注的问题，可用的卡介苗芽孢杆菌（BCG）疫苗在成人中效果不佳。因此，需要针对Mtb抗原和适当的免疫刺激佐剂的替代疫苗和递送策略，以诱导针对肺部，感染和病理的主要部位的保护性免疫。我们在这里提供证据，支持通过小鼠舌下途径进行粘膜疫苗接种，该方法是使用Mtb亚基抗原Ag85B和ESAT-6辅以糖脂α-半乳糖基神经酰胺（???±GalCer），一种有效的自然杀伤性T（NKT）细胞激动剂。接种疫苗的动物在脾脏，宫颈淋巴结和肺部表现出强烈的抗原特异性CD4和CD8 T细胞反应。通常，加入±-GalCer佐剂显着增强了这些反应，持续了50天。此外，与单纯对照组或仅接种亚单位蛋白，佐剂或BCG的对照组相比，接种过Mtb疫苗的小鼠的雾化Mtb感染导致肺和脾脏细菌负荷的显着降低。 Mtb抗原和-GalCer疫苗通过舌下途径诱导的保护作用与由抗原特异性IFN-γ3和产生IL-2的T细胞介导的TH1型免疫有关。

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