Wang Jun, Thorson Lisa, Stokes Richard W, Santosuosso Michael, Huygen Kris, Zganiacz Anna, Hitt Mary, Xing Zhou
Department of Pathology and Molecular Medicine and Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
J Immunol. 2004 Nov 15;173(10):6357-65. doi: 10.4049/jimmunol.173.10.6357.
Bacillus Calmette-Guerin (BCG) vaccine has failed to control the global tuberculosis (TB) epidemic, and there is a lack of safe and effective mucosal vaccines capable of potent protection against pulmonary TB. A recombinant replication-deficient adenoviral-based vaccine expressing an immunogenic Mycobacterium tuberculosis Ag Ag85A (AdAg85A) was engineered and evaluated for its potential to be used as a respiratory mucosal TB vaccine in a murine model of pulmonary TB. A single intranasal, but not i.m., immunization with AdAg85A provided potent protection against airway Mycobacterium tuberculosis challenge at an improved level over that by cutaneous BCG vaccination. Systemic priming with an Ag85A DNA vaccine and mucosal boosting with AdAg85A conferred a further enhanced immune protection which was remarkably better than BCG vaccination. Such superior protection triggered by AdAg85 mucosal immunization was correlated with much greater retention of Ag-specific T cells, particularly CD4 T cells, in the lung and was shown to be mediated by both CD4 and CD8 T cells. Thus, adenoviral TB vaccine represents a promising novel vaccine platform capable of potent mucosal immune protection against TB. Our study also lends strong evidence that respiratory mucosal vaccination is critically advantageous over systemic routes of vaccination against TB.
卡介苗（BCG）未能控制全球结核病（TB）的流行，并且缺乏能够有效预防肺结核的安全有效的黏膜疫苗。构建了一种表达免疫原性结核分枝杆菌抗原Ag85A的重组复制缺陷型腺病毒疫苗（AdAg85A），并在肺结核小鼠模型中评估了其作为呼吸道黏膜结核疫苗的潜力。单次鼻内接种AdAg85A而非肌肉注射，能提供比皮肤接种卡介苗更好的保护，有效抵御气道结核分枝杆菌的攻击。用Ag85A DNA疫苗进行全身初免，并用AdAg85A进行黏膜加强免疫，可进一步增强免疫保护，明显优于卡介苗接种。AdAg85黏膜免疫引发的这种卓越保护与肺中Ag特异性T细胞（特别是CD4 T细胞）的大量留存相关，且表明是由CD4和CD8 T细胞介导的。因此，腺病毒结核疫苗是一种有前景的新型疫苗平台，能够有效提供针对结核病的黏膜免疫保护。我们的研究也有力地证明，呼吸道黏膜接种疫苗相对于全身接种途径预防结核病具有关键优势。
