Minhinnick Alice, Harris Stephanie, Wilkie Morven, Peter Jonathan, Stockdale Lisa, Manjaly-Thomas Zita-Rose, Vermaak Samantha, Satti Iman, Moss Paul, McShane Helen
The Jenner Institute, University of Oxford.
School of Cancer Sciences, University of Birmingham, United Kingdom.
J Infect Dis. 2016 Mar 1;213(5):824-30. doi: 10.1093/infdis/jiv482. Epub 2015 Oct 8.
There is an urgent need for an improved tuberculosis vaccine. The lack of a validated correlate of protection slows progress in achieving this goal. A human mycobacterial challenge model, using bacille Calmette-Guérin (BCG) as a surrogate for a Mycobacterium tuberculosis challenge, would facilitate vaccine selection for field efficacy testing. Optimization of this model is required.
Healthy BCG-naive adults were assigned to receive intradermal standard-dose BCG SSI (group A), standard-dose BCG TICE (group B), high-dose BCG SSI (group C), and high-dose BCG TICE (group D). Two weeks after BCG challenge, skin biopsy of the challenge site was performed. BCG mycobacterial load was quantified by solid culture and quantitative polymerase chain reaction.
BCG was well tolerated, and reactogenicity was similar between groups, regardless of strain and dose. There was significantly greater recovery of BCG from the high-dose challenge groups, compared with standard-dose challenge. BCG strain did not significantly affect BCG recovery.
BCG challenge dose affects sensitivity of this model. We have selected high-dose BCG SSI to take forward in future challenge studies. Assessment of candidate tuberculosis vaccine effectiveness with this optimized model could contribute to vaccine selection for efficacy trials.
NCT02088892.
迫切需要改进结核病疫苗。缺乏经过验证的保护相关性指标减缓了实现这一目标的进程。一种以卡介苗（BCG）作为结核分枝杆菌攻击替代物的人类分枝杆菌攻击模型，将有助于筛选用于现场疗效测试的疫苗。需要对该模型进行优化。
将未接种过卡介苗的健康成年人分为四组，分别接受皮内注射标准剂量的卡介苗SSI（A组）、标准剂量的卡介苗TICE（B组）、高剂量的卡介苗SSI（C组）和高剂量的卡介苗TICE（D组）。卡介苗攻击两周后，对攻击部位进行皮肤活检。通过固体培养和定量聚合酶链反应对卡介苗分枝杆菌载量进行定量。
卡介苗耐受性良好，各组间的反应原性相似，与菌株和剂量无关。与标准剂量攻击组相比，高剂量攻击组的卡介苗回收率显著更高。卡介苗菌株对卡介苗回收率没有显著影响。
卡介苗攻击剂量影响该模型的敏感性。我们已选择高剂量的卡介苗SSI用于未来的攻击研究。用这种优化模型评估候选结核病疫苗的有效性有助于筛选用于疗效试验的疫苗。
NCT02088892。
