Xing Z
Department of Pathology and Molecular Medicine, and Division of Infectious Diseases, Centre for Gene Therapeutics, McMaster University, Hamilton, Canada.
Curr Pharm Des. 2001 Jul;7(11):1015-37. doi: 10.2174/1381612013397636.
Tuberculosis (TB) remains to be a leading infectious cause of death worldwide. Apparently, the current BCG vaccine that has been used for 80 years, has failed to control the TB epidemic. Hunting for improved TB vaccine formulations represents a daunting task to TB research community. Anti-TB host defense requires T cell-mediated immunity and we are in desperate need of enhanced understanding of how to develop a new generation of TB vaccines that are able to provoke potent and long-lasting protective cell-mediated immunity, different from almost all of the vaccines currently in use. It is of importance to successful TB vaccine development to identify the key cellular and molecular events governing the generation of anti-TB immunity, but unfortunately little has been understood as to why 90% of infected humans never develop active TB. However, waiting would not help us to win the battle and an ever-intensifying effort is being made to develop various new formulations according to the immunology that we have been learning, in large part, from experimental models. This review article attempts to unite the current understanding of anti-TB immunity with the rational design of anti-TB vaccines. It examines what may have confounded the immunogenicity of current BCG vaccine and the major obstacles to successful development of TB vaccines. It also discusses about antigen presentation, activation of Th1 and Tc1 cells, anti-TB immune effectors and the generation of memory T cells. The vaccine section describes four types of major TB vaccines under development: mycobacterial-, subunit-, plasmid DNA- and viral-based vaccines. A special section is dedicated to the rationale and current design of cytokine-based adjuvant formulations for TB vaccines. We also take this opportunity to introduce our recent development in cytokine transgene adjuvanted BCG vaccination and recombinant adenoviral-based TB vaccines.
结核病（TB）仍然是全球主要的感染性致死原因。显然，已使用80年的现有卡介苗未能控制结核病的流行。寻找改进的结核病疫苗配方对结核病研究界来说是一项艰巨的任务。抗结核宿主防御需要T细胞介导的免疫，我们迫切需要更深入地了解如何开发新一代结核病疫苗，使其能够激发强大且持久的保护性细胞介导免疫，这与目前几乎所有正在使用的疫苗不同。确定控制抗结核免疫产生的关键细胞和分子事件对于成功开发结核病疫苗至关重要，但遗憾的是，对于为何90%的感染者从未发展为活动性结核病，我们了解甚少。然而，等待无助于我们赢得这场战斗，并且正在根据我们在很大程度上从实验模型中学到的免疫学知识，不断加大力度开发各种新配方。这篇综述文章试图将目前对抗结核免疫的理解与抗结核疫苗的合理设计结合起来。它研究了可能混淆现有卡介苗免疫原性的因素以及结核病疫苗成功开发的主要障碍。它还讨论了抗原呈递、Th1和Tc1细胞的激活、抗结核免疫效应器以及记忆T细胞的产生。疫苗部分描述了正在研发的四种主要类型的结核病疫苗：基于分枝杆菌的疫苗、亚单位疫苗、质粒DNA疫苗和病毒载体疫苗。一个特别的部分专门讨论了基于细胞因子的结核病疫苗佐剂配方的原理和当前设计。我们还借此机会介绍我们在细胞因子转基因佐剂卡介苗接种和基于重组腺病毒的结核病疫苗方面的最新进展。
