Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2010 Oct 29;5(10):e13773. doi: 10.1371/journal.pone.0013773.
M. bovis Bacille Calmette-Guérin (BCG), currently the only available vaccine against tuberculosis (TB), fails to adequately protect individuals from active and latent TB infection. New vaccines are desperately needed to decrease the worldwide burden of TB.
We created a recombinant strain of BCG that overproduces an L,D-transpeptidase in order to alter the bacterial peptidoglycan layer and consequently increase the ability of this immunogen to protect against virulent M. tuberculosis (Mtb). We demonstrate that this novel recombinant BCG protects mice against virulent Mtb at least as well as control BCG, as measured by its ability to reduce bacterial burden in lungs and spleen, reduce lung histopathology, and prolong survival. A nutrient starved recombinant BCG preparation, while offering comparable protection, elicited a response characterized by elevated levels of select Th1 cytokines.
Recombinant BCG overexpressing a L,D-transpeptidase that is nutrient starved elicits a stronger Th1 type response and is at least as protective as parent BCG. Results from this study suggest that nutrient starvation treatment of live BCG vaccines should be further investigated as a way to increase host induction of Th-1 related cytokines in the development of experimental anti-TB vaccines.
牛型分枝杆菌卡介苗（BCG）是目前唯一可用于预防结核病（TB）的疫苗，但不能充分保护个体免受活动性和潜伏性 TB 感染。迫切需要新的疫苗来降低全球结核病负担。
我们创建了一种重组 BCG 菌株，该菌株过度表达 L,D-转肽酶，以改变细菌肽聚糖层，从而提高这种免疫原预防毒力结核分枝杆菌（Mtb）的能力。我们证明，这种新型重组 BCG 能够像对照 BCG 一样保护小鼠免受毒力 Mtb 的侵害，其保护作用可以通过减少肺部和脾脏的细菌负荷、减少肺部组织病理学变化和延长存活时间来衡量。饥饿营养的重组 BCG 制剂虽然提供了相当的保护作用，但引发了一种以选择性 Th1 细胞因子水平升高为特征的反应。
过度表达 L,D-转肽酶的饥饿营养重组 BCG 引发了更强的 Th1 型反应，其保护作用与亲本 BCG 至少一样。这项研究的结果表明，应该进一步研究活 BCG 疫苗的饥饿营养处理方法，作为增加宿主在实验性抗 TB 疫苗中诱导 Th1 相关细胞因子的一种方式。
