Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy.

Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy.
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DOI:
10.1371/journal.pone.0019840
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
McShane H
McShane H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Minassian AM;Ronan EO;Poyntz H;Hill AV;McShane H

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迫切需要一种预防结核病(TB)的免疫学相关性,以便在临床试验中评估候选结核病疫苗。开发结核分枝杆菌人类挑战模型(M.tb)可以促进这种相关性的检测(S)。在这里,我们提出了一种新颖的卡介苗(BCG)体内攻击模型,该模型使用卡介苗免疫作为结核分枝杆菌感染的替代。利用小鼠的耳朵作为人类皮肤的替代品,已经开发出培养和定量PCR方法来定量皮肤中的卡介苗。使用该模型评估了候选结核疫苗对卡介苗皮肤挑战的保护能力,结果表明,对卡介苗皮肤挑战的保护可以预测卡介苗对气溶胶结核分枝杆菌挑战的效力。将这些发现转化为人类卡介苗挑战模型,可以更快地评估和降低候选结核病疫苗的选择,并最终识别与保护相关的免疫因素。
There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection.
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