Evaluation of a human BCG challenge model to assess antimycobacterial immunity induced by BCG and a candidate tuberculosis vaccine, MVA85A, alone and in combination.
Evaluation of a human BCG challenge model to assess antimycobacterial immunity induced by BCG and a candidate tuberculosis vaccine, MVA85A, alone and in combination.
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DOI：
10.1093/infdis/jit647
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发表时间：
2014-04-15
期刊：
影响因子：
--
通讯作者：
McShane H
中科院分区：
文献类型：
--
作者：
Harris SA;Meyer J;Satti I;Marsay L;Poulton ID;Tanner R;Minassian AM;Fletcher HA;McShane H
背景：迫切需要一种新的疫苗来对抗结核病。 然而，如果没有相关的保护，选择疫苗进行大规模的有效性试验是困难的。使用卡介苗（BCG）作为人类结核分枝杆菌挑战的替代物是一种新的模型，可以帮助选择。方法：将健康成人分为A组和B组（未接种过卡介苗）或C组和D组（接种过卡介苗）。 B组和D组接受候选结核疫苗MVA 85 A。在接受MVA85 A治疗4周后，参与者接受皮内卡介苗激发。攻毒后2周对攻毒部位进行皮肤活检，并通过培养和定量聚合酶链反应（qPCR）对BCG负荷进行定量。结果：有卡介苗接种史的志愿者表现出一定程度的保护性免疫力，与既往未接种卡介苗的志愿者相比，无论MVA85A状态如何，其卡介苗负荷量均较低。 MVA85A后峰值应答时的抗分枝杆菌免疫力与qPCR检测的BCG载量之间存在显著的负相关。结论：我们的结果支持先前的发现，即BCG激发模型能够检测疫苗接种诱导的抗分枝杆菌免疫的差异，并有助于选择候选结核疫苗进行田间效力测试。 临床试验注册NCT01194180。
Background. A new vaccine is urgently needed to combat tuberculosis. However, without a correlate of protection, selection of the vaccines to take forward into large-scale efficacy trials is difficult. Use of bacille Calmette-Guérin (BCG) as a surrogate for human Mycobacterium tuberculosis challenge is a novel model that could aid selection. Methods. Healthy adults were assigned to groups A and B (BCG-naive) or groups C and D (BCG-vaccinated). Groups B and D received candidate tuberculosis vaccine MVA85A. Participants were challenged with intradermal BCG 4 weeks after those who received MVA85A. Skin biopsies of the challenge site were taken 2 weeks post challenge and BCG load quantified by culture and quantitative polymerase chain reaction (qPCR). Results. Volunteers with a history of BCG showed some degree of protective immunity to challenge, having lower BCG loads compared with volunteers without prior BCG, regardless of MVA85A status. There was a significant inverse correlation between antimycobacterial immunity at peak response after MVA85A and BCG load detected by qPCR. Conclusion. Our results support previous findings that this BCG challenge model is able to detect differences in antimycobacterial immunity induced by vaccination and could aid in the selection of candidate tuberculosis vaccines for field efficacy testing. Clinical Trials Registration NCT01194180.
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影响因子：
3.7
作者：
Minassian AM;Ronan EO;Poyntz H;Hill AV;McShane H
通讯作者：
McShane H
影响因子：
--
作者：
Fletcher, Helen A.;Tanner, Rachel;McShane, Helen
通讯作者：
McShane, Helen
影响因子：
9.4
作者：
Talbot, EA;Williams, DL;Frothingham, R
通讯作者：
Frothingham, R
影响因子：
100.3
作者：
Sauerwein, Robert W.;Roestenberg, Meta;Moorthy, Vasee S.
通讯作者：
Moorthy, Vasee S.
影响因子：
5.5
作者：
Pathan, Ansar A.;Minassian, Angela M.;Sander, Clare R.;Rowland, Rosalind;Porter, David W.;Poulton, Ian D.;Hill, Adrian V. S.;Fletcher, Helen A.;McShane, Helen
通讯作者：
McShane, Helen