Optimization of a Human Bacille Calmette-Guérin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity.
Optimization of a Human Bacille Calmette-Guérin Challenge Model: A Tool to Evaluate Antimycobacterial Immunity.
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DOI：
10.1093/infdis/jiv482
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
McShane H
中科院分区：
文献类型：
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作者：
Minhinnick A;Harris S;Wilkie M;Peter J;Stockdale L;Manjaly-Thomas ZR;Vermaak S;Satti I;Moss P;McShane H
背景。迫切需要改进结核病疫苗。缺乏有效的相关保护减缓了实现这一目标的进程。使用卡介苗（BCG）作为结核分枝杆菌攻击的替代物的人类分枝杆菌攻击模型，将有助于为实地效力试验选择疫苗。需要对该模型进行优化。方法。未感染BCG的健康成人分别接受皮内标准剂量BCG SSI （A组）、标准剂量BCG TICE （B组）、高剂量BCG SSI （C组）和高剂量BCG TICE （D组）。卡介苗激射后2周，对激射部位进行皮肤活检。采用固体培养法和定量聚合酶链反应法定量卡介苗分枝杆菌载量。结果。卡介苗耐受性良好，无论菌株和剂量，两组间的反应原性相似。与标准剂量攻毒组相比，高剂量攻毒组的卡介苗回收率显著提高。卡介苗菌株对卡介苗恢复无显著影响。结论。卡介苗攻毒剂量影响该模型的敏感性。我们选择了高剂量BCG SSI用于未来的挑战研究。利用优化后的模型评价结核候选疫苗的有效性，有助于临床疗效试验的疫苗选择。临床试验注册，NCT02088892。
Background. 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. Methods. 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. Results. 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. Conclusions. 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. Clinical Trials Registration. NCT02088892.