BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies
BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies
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DOI：
10.1016/s0140-6736(02)08353-8
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发表时间：
2002-04-20
期刊：
影响因子：
168.9
通讯作者：
Dockrell, HM
中科院分区：
文献类型：
--
作者：
Black, GF;Weir, RE;Dockrell, HM
BCG疫苗对肺结核的有效性因人群而异，在马拉维没有保护作用，但在英国有50-80%的保护作用。为了研究这些差异背后的机制，建立了随机对照研究，以测量两个population.Methods 483名青少年和年轻成人在马拉维和180名青少年在英国的疫苗诱导的免疫反应的分枝杆菌抗原进行了测试干扰素γ（IFN-γ）在全血测定中对结核分枝杆菌纯化蛋白衍生物（PPD）的应答，以及对结核菌素PPD的迟发型超敏反应（DTH）皮肤试验应答，接种BCG前后1年（Glaxo 1077）疫苗接种或安慰剂或无疫苗。结果显示IFN-γ和DTH反应的随机个体的百分比在马拉维高于英国疫苗接种前-即，IFN-γ为61%（331/546）与22%（47/213），DTH为46%（236/517）与13%（27/211）。IFN-γ应答在英国比在马拉维增加更多，分别有83%（101/122）和78%（251/321）的接种组应答，在接种后1年两个人群中的分布相似。在这两个地方接种疫苗后，DTH反应增加，但在英国比马拉维更大程度上。IFN-γ和DTH反应是密切相关的，除了疫苗之间在Malawi.Interpretation的BCG-归因于增加IFN-γ对结核分枝杆菌PPD的反应，从接种疫苗前到1年后的幅度，相关性更好地与已知的水平的保护诱导免疫接种卡介苗比的IFN-γ或DTH反应的绝对值接种疫苗后。由于暴露于环境分枝杆菌而引起的不同致敏性可能是观察到的人群间BCG保护差异的最重要决定因素。
Background The efficacy of BCG vaccines against pulmonary tuberculosis varies between populations, showing no protection in Malawi but 50-80% protection in the UK. To investigate the mechanism underlying these differences, randomised controlled studies were set up to measure vaccine-induced immune responsiveness to mycobacterial antigens in both populations.Methods 483 adolescents and young adults in Malawi and 180 adolescents in the UK were tested for interferon-gamma (IFN-gamma) response to M tuberculosis purified protein derivative (PPD) in a whole blood assay, and for delayed type hypersensitivity (DTH) skin test response to tuberculin PPD, before and 1 year after receiving BCG (Glaxo 1077) vaccination or placebo or no vaccine.Findings The percentages of the randomised individuals who showed IFN-gamma and DTH responses were higher in Malawi than in the UK pre-vaccination-ie, 61% (331/546) versus 22% (47/213) for IFN-gamma and 46% (236/517) versus 13% (27/211) for DTH. IFN-gamma responses increased more in the UK than in Malawi, with 83% (101/122) and 78% (251/321) respectively of the vaccinated groups responding, with similar distributions in the two populations 1 year post-vaccination. The DTH response increased following vaccination in both locations, but to a greater extent in the UK than Malawi. The IFN-gamma and DTH responses were strongly associated, except among vaccines in Malawi.Interpretation The magnitude of the BCG-attributable increase in IFN-gamma responsiveness to M tuberculosis PPD, from before to 1 year post-vaccination, correlates better with the known levels of protection induced by immunisation with BCG than does the absolute value of the IFN-gamma or DTH response after vaccination. It is likely that differential sensitisation due to exposure to environmental mycobacteria is the most important determinant of the observed differences in protection by BCG between populations.