Department of Bacteriology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Vaccine. 2011 Sep 16;29(40):6881-7. doi: 10.1016/j.vaccine.2011.07.051. Epub 2011 Jul 29.
Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most often used vaccine worldwide and sole vaccine against tuberculosis. BCG is protective against severe form of childhood tuberculosis but less or not protective to adult pulmonary tuberculosis. Therefore, improved vaccination strategies and development of new tuberculosis vaccines are urgent demands. For those purposes, appropriate animal models that reflect human are critically useful. However, in animal models, BCG vaccination protects well against subsequent challenge of Mycobacterium tuberculosis. In this study we evaluated the duration of protective efficacy of the BCG vaccination in mice over time and found that efficacy was diminished 40 weeks after vaccination. The aged mice older than 45 weeks are protected sufficiently after the vaccination with BCG, suggesting that loss of its efficacy is not dependent on the age of mice but rather depends on the period from vaccination. The loss of protection occurred in TH1 polarized STAT6 deficient mice despite the maintenance of interferon (IFN)-gamma production activity of lymph node cells and splenic CD4(+) T cells against M. tuberculosis antigens. Our data suggest that the duration from vaccination may explain the variation in BCG efficacy against adult pulmonary tuberculosis.
牛分枝杆菌卡介苗（BCG）是世界上应用最广泛的疫苗，也是唯一用于预防结核病的疫苗。BCG 对儿童结核病的严重形式具有保护作用，但对成人肺结核的保护作用较小或没有。因此，迫切需要改进疫苗接种策略和开发新的结核病疫苗。为此，能够反映人类疾病的合适动物模型是非常有用的。然而，在动物模型中，BCG 疫苗接种对随后的结核分枝杆菌感染具有良好的保护作用。在这项研究中，我们评估了 BCG 疫苗在小鼠中的保护效力随时间的变化，并发现接种后 40 周保护效力降低。接种 BCG 后，年龄大于 45 周的老年小鼠得到充分保护，这表明其效力的丧失不是取决于小鼠的年龄，而是取决于接种后的时间。尽管淋巴结细胞和脾 CD4(+)T 细胞针对结核分枝杆菌抗原的干扰素（IFN）-γ产生活性得到维持，TH1 极化 STAT6 缺陷小鼠的保护作用仍然丧失。我们的数据表明，从接种到发病的时间可能解释了 BCG 对成人肺结核的疗效差异。
