Khan Arshad, Singh Shailbala, Galvan Gloria, Jagannath Chinnaswamy, Sastry K Jagannadha
Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, TX 77030, USA.
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Vaccines (Basel). 2017 Dec 6;5(4):47. doi: 10.3390/vaccines5040047.
Infection by (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 (α-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 α-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 naïve 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-γ and IL-2 producing T cells.
结核分枝杆菌（Mtb）感染仍然是全球主要关注的问题，现有的卡介苗（BCG）在成人中的效力不佳。因此，需要替代疫苗和递送策略，聚焦于Mtb抗原和合适的免疫刺激佐剂，以诱导针对肺部（感染和病理的主要部位）的保护性免疫。我们在此展示证据，支持在小鼠中通过舌下途径进行黏膜疫苗接种，使用亚单位Mtb抗原Ag85B和ESAT-6，并佐以糖脂α-半乳糖神经酰胺（α-GalCer），一种有效的自然杀伤T（NKT）细胞激动剂。接种疫苗的动物在脾脏、颈部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。一般来说，加入α-GalCer佐剂显著增强了这些反应，且持续超过50天。此外，与未接种的对照小鼠或仅接种亚单位蛋白、佐剂或卡介苗的小鼠相比，对接种疫苗的小鼠进行雾化Mtb感染后，其肺部和脾脏的细菌载量显著降低。通过舌下途径的Mtb抗原和α-GalCer疫苗诱导的保护作用与由产生抗原特异性IFN-γ和IL-2的T细胞介导的TH1型免疫相关。
