Immunogenicity and protection induced by Mycobacterium tuberculosis mce-2 and mce-3 mutants in a Balb/c mouse model of progressive pulmonary tuberculosis
Immunogenicity and protection induced by Mycobacterium tuberculosis mce-2 and mce-3 mutants in a Balb/c mouse model of progressive pulmonary tuberculosis
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DOI：
10.1016/j.vaccine.2005.11.051
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发表时间：
2006-03-20
期刊：
影响因子：
5.5
通讯作者：
Pando, RH
中科院分区：
文献类型：
--
作者：
Aguilar, LD;Infante, E;Pando, RH
由哺乳动物细胞进入（mce）基因编码的分枝杆菌蛋白允许细胞侵入宿主。结核分枝杆菌 mce-2 和 mce-3 突变体损害了 mce 蛋白的合成，并且在 BALB/c 小鼠中减弱。与亲本 H37Rv 菌株相比，具有任一 mce 突变体的 Balb/c 小鼠气管内感染可诱导较低但渐进的 IFN-γ 和 TNF-α 产生，以及更大的迟发型超敏反应 (DTH) 反应。当用作皮下疫苗时，在攻击之前，两种突变体在 Balb/c 和免疫缺陷裸鼠中的减毒效果都比 BCG 更强。用分枝杆菌培养滤液抗原 (CFA) 或免疫显性抗原 (ESAT-6、Ag85) 刺激的 mce 突变体疫苗接种小鼠的淋巴结和脾脏细胞悬浮液比接种 BCG 的动物产生更多的 INF-γ。用作皮下疫苗时，在气管内攻击高毒力结核分枝杆菌菌株（北京代码9501000）前60天，两种突变株诱导的保护水平均高于卡介苗；接种 mce-2 和 mce-3 突变体的小鼠分别有 72% 和 63% 在攻击后存活了 16 周，而接种 BCG 的小鼠只有 30% 存活。同样，与接种卡介苗的小鼠相比，接种这两种突变体的小鼠的组织损伤（肺炎）较少，菌落形成单位（CFU）较低。这些数据表明，缺乏mce-2和-3基因表达会降低活疫苗的毒力并增加其免疫原性，有利于它们预防结核病的能力，这比卡介苗所提供的保护更好。 (c) 2005 Elsevier Ltd. 保留所有权利。
Mycobacterial proteins coded by the mammalian cell entry (mce) genes allow for cell invasion into the host. The Mycobacterium tuberculosis mce-2 and mce-3 mutants have impaired synthesis of mce proteins and are attenuated in BALB/c mice. Intra-tracheal infection of Balb/c mice with either mce mutant induced lower but progressive production of IFN-gamma and TNF-alpha, as well as larger delayed type hypersensitivity (DTH) reactions, than their parental H37Rv strain. When used as a subcutaneous vaccine and, before challenge, both mutants were more attenuated than BCG in Balb/c and immunodeficient nude mice. Cell suspensions from lymph nodes and spleen from mce mutant vaccinated mice stimulated with mycobacterial culture filtrate antigens (CFA) or immunodominant antigens (ESAT-6, Ag85) produced more INF-gamma than BCG-vaccinated animals. Used as subcutaneous vaccines, 60 days before intra-tracheal challenge with the hypervirulent strain of M. tuberculosis (Beijing code 9501000), both mutants induced a higher level of protection than BCG; 72% and 63% of the mice vaccinated with the mce-2 and mce-3 mutants, respectively, survived for 16 weeks after the challenge as compared to 30% of those vaccinated with BCG. Likewise, there was less tissue damage (pneumonia) and lower colony forming units (CFU) in the mice vaccinated with either of the two mutants as compared to the findings in mice vaccinated with BCG. These data suggest that lack of mce-2 and -3 gene expression decreases virulence and increases immunogenicity of live vaccines, favouring their ability to protect against tuberculosis, which was better than the protection conferred by BCG. (c) 2005 Elsevier Ltd. All rights reserved.