Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice.
Mucosal immunization with recombinant heparin-binding haemagglutinin adhesin suppresses extrapulmonary dissemination of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in infected mice.
复制标题
DOI：
10.1016/j.vaccine.2007.12.005
复制
发表时间：
2008-02
期刊：
影响因子：
5.5
通讯作者：
H. Kohama;M. Umemura;Y. Okamoto;A. Yahagi;H. Goga;T. Harakuni;G. Matsuzaki;T. Arakawa
中科院分区：
文献类型：
--
作者：
H. Kohama;M. Umemura;Y. Okamoto;A. Yahagi;H. Goga;T. Harakuni;G. Matsuzaki;T. Arakawa
一般认为细胞免疫在抵抗结核分枝杆菌（一种细胞内病原体）的保护中起关键作用。然而，最近，越来越多的报告表明体液免疫对分枝杆菌感染的重要贡献。自从M.结核病在肺中建立其原发性损害，通过粘膜免疫方案在气道中诱导体液免疫可提供针对结核病的保护性免疫。在这项研究中，分枝杆菌肝素结合血凝素粘附素（HBHA）被用作免疫抗原，因为HBHA是肺上皮细胞感染和分枝杆菌肺外播散所需的重要毒力因子。研究了酵母表达的重组（r）HBHA与粘膜佐剂霍乱毒素（CT）联合给药的鼻内免疫对诱导体液和细胞免疫的影响，并评价了其对牛分枝杆菌卡介苗（BCG）肺部攻毒感染的保护作用。免疫小鼠的血清和气道中诱导出特异性抗体，该抗体特异性识别M.牛卡介苗。BCG肺感染后，免疫小鼠肺中对分枝杆菌抗原的Th1型免疫也增强。此外，免疫抑制肺BCG感染后脾脏中的细菌负荷。这些结果表明，由基于HBHA的粘膜疫苗诱导的全身和局部体液免疫损害肺外播散，从而提供针对分枝杆菌感染的免疫保护。
It is generally accepted that cellular immunity plays a critical role in the protection against Mycobacterium tuberculosis, an intracellular pathogen. Recently, however, an increasing number of reports indicate the important contribution of humoral immunity against mycobacterial infection. Since M. tuberculosis establishes its primary lesion in the lung, induction of humoral immunity in the airway tract by mucosal immunization regime could provide protective immunity against tuberculosis. In this study, mycobacterial heparin-binding haemagglutinin adhesin (HBHA) was used as an immunization antigen because HBHA is an essential virulence factor required for the infection of lung epithelial cells and extrapulmonary dissemination of mycobacteria. The effects of intranasal immunization with a yeast-expressed recombinant (r) HBHA co-administered with a mucosal adjuvant cholera toxin (CT) on the induction of humoral and cellular immunity were examined, and its protective efficacy against pulmonary challenge infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG) was evaluated. HBHA-specific antibodies were induced in serum and airway tract of immunized mice, which specifically recognized native HBHA expressed on M. bovis BCG. Th1-type immunity against mycobacterial antigens was also enhanced in the lung of immunized mice after pulmonary BCG infection. Furthermore, the immunization suppressed bacterial load in the spleen after pulmonary BCG infection. These results indicate that systemic and local humoral immunity induced by the HBHA-based mucosal vaccine impairs extrapulmonary dissemination, thus providing immune protection against mycobacterial infection.