卡介苗诱导的对分枝杆菌抗原的γ干扰素反应增加以及卡介苗接种在马拉维和英国的效果：两项随机对照研究

BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies.

作者信息

Black Gillian F, Weir Rosemary E, Floyd Sian, Bliss Lyn, Warndorff David K, Crampin Amelia C, Ngwira Bagrey, Sichali Lifted, Nazareth Bernadette, Blackwell Jenefer M, Branson Keith, Chaguluka Steven D, Donovan Linda, Jarman Elizabeth, King Elizabeth, Fine Paul E M, Dockrell Hazel M

机构信息

Karonga Prevention Study, Chilumba, Malawi.

出版信息

Lancet. 2002 Apr 20;359(9315):1393-401. doi: 10.1016/S0140-6736(02)08353-8.

DOI:10.1016/S0140-6736(02)08353-8

PMID:11978337

Abstract

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 vaccinees 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.

摘要

背景

卡介苗对肺结核的疗效在不同人群中有所差异，在马拉维未显示出保护作用，而在英国有50%-80%的保护率。为研究这些差异背后的机制，开展了随机对照研究，以测量这两个人群中疫苗诱导的对分枝杆菌抗原的免疫反应性。

方法

在马拉维的483名青少年和青年以及英国的180名青少年接种卡介苗（葛兰素1077）、安慰剂或不接种疫苗之前及之后1年，通过全血检测法检测他们对结核分枝杆菌纯蛋白衍生物（PPD）的干扰素-γ（IFN-γ）反应，并检测对结核菌素PPD的迟发型超敏反应（DTH）皮肤试验反应。

研究结果

接种疫苗前，显示IFN-γ和DTH反应的随机个体百分比在马拉维高于英国，即IFN-γ反应分别为61%（331/546）和22%（47/213），DTH反应分别为46%（236/517）和13%（27/211）。IFN-γ反应在英国的增加幅度大于马拉维，接种疫苗组的反应率分别为83%（101/122）和78%（251/321），接种疫苗后1年，这两个人群的分布相似。两个地区接种疫苗后DTH反应均增加，但在英国的增加幅度大于马拉维。IFN-γ和DTH反应密切相关，但马拉维的疫苗接种者除外。