McMurray David N
Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, Reynolds Medical Building, Room 463, College Station, TX 77843-1114, USA.
Int J Parasitol. 2003 May;33(5-6):547-54. doi: 10.1016/s0020-7519(03)00061-4.
The growing pandemic of human tuberculosis has not been affected significantly by the widespread use of the only currently available vaccine, bacille Calmette Guerin. Bacille Calmette Guerin protects uniformly against serious paediatric forms of tuberculosis and against adult pulmonary tuberculosis in some parts of the world, but there are clearly populations in high-burden countries which do not benefit from the current vaccination regimen. New tuberculosis vaccines will be essential for the ultimate control of this ancient disease. Research over the past 10 years has produced literally hundreds of new tuberculosis vaccine candidates representing all of the major vaccine design strategies; protein/peptide vaccines in adjuvants, DNA vaccines, naturally and rationally attenuated strains of mycobacteria, recombinant mycobacteria and other living vaccine vectors expressing genes coding for immunodominant mycobacterial antigens, and non-peptide vaccines. Many of these vaccines have been tested for immunogenicity and protective efficacy in mouse and guinea pig models of low-dose pulmonary tuberculosis. In addition, alternative routes of tuberculosis vaccine delivery (e.g. oral, respiratory, gene gun) and various combinations of priming or boosting an experimental vaccine with bacille Calmette Guerin have been examined in relevant animal models. One of the most promising of these vaccines is currently in Phase I trials in human subjects, and others are expected to follow in the near future. This review will summarise the most recent progress made toward the development and preclinical evaluation of novel vaccines for human tuberculosis.
目前唯一可用的疫苗卡介苗的广泛使用,并未对日益蔓延的人类结核病疫情产生显著影响。卡介苗能有效预防严重的儿童结核病形式,并在世界某些地区预防成人肺结核,但在高负担国家显然有一些人群无法从当前的疫苗接种方案中受益。新型结核病疫苗对于最终控制这种古老疾病至关重要。过去10年的研究产生了数百种新的结核病疫苗候选物,涵盖了所有主要的疫苗设计策略;佐剂中的蛋白质/肽疫苗、DNA疫苗、天然和合理减毒的分枝杆菌菌株、重组分枝杆菌以及表达编码免疫显性分枝杆菌抗原基因的其他活疫苗载体,还有非肽疫苗。其中许多疫苗已在低剂量肺结核的小鼠和豚鼠模型中进行了免疫原性和保护效力测试。此外,还在相关动物模型中研究了结核病疫苗的替代给药途径(如口服、呼吸道、基因枪),以及用卡介苗启动或加强实验性疫苗的各种组合。这些疫苗中最有前景的一种目前正在进行人体I期试验,预计其他疫苗也将在不久的将来跟进。本综述将总结在人类结核病新型疫苗的研发和临床前评估方面取得的最新进展。