The Jenner Institute, University of Oxford, Oxford, United Kingdom.
PLoS One. 2011;6(5):e19840. doi: 10.1371/journal.pone.0019840. Epub 2011 May 24.
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.
迫切需要一种针对结核病 (TB) 的免疫保护相关物，以便在临床试验中评估候选 TB 疫苗。开发结核分枝杆菌 (M.tb) 的人体挑战模型可以促进对这种相关性的检测。在这里，我们提出了一种新的卡介苗 (BCG) 体内挑战模型，使用 BCG 免疫作为 M.tb 感染的替代物。已经开发了培养和定量聚合酶链反应方法来定量检测小鼠耳部皮肤中的 BCG，以模拟人类皮肤。使用该模型评估了候选 TB 疫苗对 BCG 皮肤挑战的保护能力，结果表明，对 BCG 皮肤挑战的保护作用可预测 BCG 疫苗对气溶胶 M.tb 挑战的疗效。将这些发现转化为人体 BCG 挑战模型，可以更快速地评估和筛选候选 TB 疫苗，并最终确定保护的免疫相关性。
