Aeras, 1405 Research Blvd., Rockville, MD 20850, USA.
Vaccine. 2013 Apr 18;31 Suppl 2:B223-6. doi: 10.1016/j.vaccine.2012.11.081.
There are nearly ten million new cases and 1.4 million deaths from tuberculosis (TB) each year, and the 90-year old bacille calmette-guérin (BCG) vaccine in widespread use appears to have minimal impact on the worldwide incidence, despite demonstrating reasonable efficacy against complications of infant TB and death. Novel vaccine development has accelerated in the past ten years, with at least 16 candidates entering human trials, and a few vaccines have entered into Phase 2b efficacy studies. However, different vaccines may be needed due to the varying disease states (naïve, latently infected, or active), the ages affected (infants, adolescents and young adults, the elderly), and patient health status (HIV and immunocompromised patients especially). Modeling has shown that mass vaccination of latently infected populations, especially adolescents and young adults, will likely have the largest impact on new infection rates. At present, research and development of TB vaccines is hampered by the lack of validated animal models, the absence of correlates of immunity and a human challenge model, as well as by the size and cost of Proof-of-Concept clinical trials. Nonetheless, ongoing research and clinical studies should remove many of these barriers over the next five years, and lead to an increased understanding of the pathogenicity of Mycobacterium tuberculosis and what may constitute protective immunity during various stages of infection and disease.
每年有近 1000 万例新发病例和 140 万人死于结核病（TB），尽管卡介苗（BCG）疫苗在广泛使用中对婴儿结核病并发症和死亡的疗效合理，但对全球发病率的影响似乎微乎其微。新型疫苗的开发在过去十年中加速，至少有 16 种候选疫苗进入人体试验，少数疫苗已进入 2b 期疗效研究。然而，由于疾病状态（初发、潜伏感染或活动）、受影响的年龄（婴儿、青少年和青年、老年人）以及患者健康状况（HIV 和免疫功能低下患者）的不同，可能需要不同的疫苗。建模表明，大规模接种潜伏感染人群，尤其是青少年和青年，可能对新感染率产生最大影响。目前，TB 疫苗的研究和开发受到缺乏经过验证的动物模型、缺乏免疫相关性和人体挑战模型以及概念验证临床试验的规模和成本的阻碍。尽管如此，未来五年内，正在进行的研究和临床研究应该会消除这些障碍中的许多障碍，并提高对结核分枝杆菌致病性以及在感染和疾病的各个阶段可能构成保护性免疫的认识。
