Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis
Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis
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DOI：
10.1038/nm859
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发表时间：
2003-05-01
期刊：
影响因子：
82.9
通讯作者：
Cole, ST
中科院分区：
文献类型：
--
作者：
Pym, AS;Brodin, P;Cole, ST
活结核病疫苗牛分枝杆菌BCG（卡介苗）和田鼠分枝杆菌都缺乏有效的分泌型T细胞抗原ESAT-6（6-kDa早期分泌抗原靶标）和CFP-10（10-kDa培养滤液蛋白）。这是在缺失-1（RD 1）基因座区域中独立缺失的结果，该区域在结核分枝杆菌复合体的毒性成员中是完整的。为了提高它们的免疫原性和保护能力，我们用含有esxA和esxB基因（分别编码ESAT-6和CFP-10）以及可变数量的侧翼基因的不同构建体补充了这两种疫苗。只有重新引入完整的基因座，包括至少11个基因，导致抗原的完全分泌，并导致特异性ESAT-6依赖性免疫应答;这表明侧翼基因编码分泌装置。重组BCG：：RD 1 - 2F 9株免疫小鼠和豚鼠，对M.与仅用BCG免疫的对照动物相比，显示出较不严重的病理学和减少的病原体传播。
The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guerin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (RD1) locus, which is intact in virulent members of the Mycobacterium tuberculosis complex. To increase their immunogenicity and protective capacity, we complemented both vaccines with different constructs containing the esxA and esxB genes, which encode ESAT-6 and CFP-10 respectively, as well as a variable number of flanking genes. Only reintroduction of the complete locus, comprising at least 11 genes, led to full secretion of the antigens and resulted in specific ESAT-6-dependent immune responses; this suggests that the flanking genes encode a secretory apparatus. Mice and guinea pigs vaccinated with the recombinant strain BCG:: RD1-2F9 were better protected against challenge with M. tuberculosis, showing less severe pathology and reduced dissemination of the pathogen, as compared with control animals immunized with BCG alone.