Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity
Mucosal administration of Ag85B-ESAT-6 protects against infection with Mycobacterium tuberculosis and boosts prior bacillus Calmette-Guerin immunity
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DOI：
10.4049/jimmunol.177.9.6353
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发表时间：
2006-11-01
影响因子：
4.4
通讯作者：
Andersen, Peter
中科院分区：
文献类型：
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作者：
Dietrich, Jes;Andersen, Claire;Andersen, Peter
我们研究了一种由粘膜佐剂LTK63和AgAg85B-ESAT-6组成的结核分枝杆菌疫苗(M.tb)的鼻腔给药情况。LTK63/Ag85B-ESAT-6在二甲基二十八烷基溴化铵/单磷脂A中接种后，由分泌干扰素的CD4细胞介导的Th1反应强烈而持久，对结核病具有持久的保护作用，相当于卡介苗(BCG)或Ag85B-ESAT-6。由于新疫苗策略的一个关键因素是增强卡介苗来源的免疫，我们还测试了LTK63/Ag85BESAT-6能否在卡介苗免疫小鼠中作为卡介苗增强疫苗。我们发现，接种LTK63/Ag85B-ESAT-6疫苗可显著增强卡介苗刺激的免疫力。与未接种卡介苗的小鼠相比，我们观察到，在LTK63/Ag85B-ESAT-6增强免疫的小鼠中，感染结核分枝杆菌的小鼠肺中抗结核分枝杆菌特异性的CD4T细胞显著增加。这与LTK63/Ag85B-ESAT-6增强的小鼠与卡介苗接种的小鼠相比，对结核分枝杆菌的保护作用显著增强有关。因此，LTK63/Ag85B-ESAT-6是一种有效的结核病预防疫苗，具有很强的增强既往卡介苗免疫的能力。
We have examined the intranasal administration of a vaccine against Mycobacterium tuberculosis (M.tb) consisting of the mucosal adjuvant LTK63 and the Ag Ag85B-ESAT-6. Vaccination with LTK63/Ag85B-ESAT-6 gave a strong and sustained Th1 response mediated by IFN-gamma-secreting CD4 cells, which led to long-lasting protection against tuberculosis, equivalent to that observed with bacillus Calmette-Guerin (BCG) or Ag85B-ESAT-6 in dimethyldioctadecylammonium bromide/monophosphoryl lipid A. Because a crucial element of novel vaccine strategies is the ability to boost BCG-derived immunity, we also tested whether LTK63/Ag85BESAT-6 could act as a BCG booster vaccine in BCG-vaccinated mice. We found that vaccinating with LTK63/Ag85B-ESAT-6 strongly boosted prior BCG-stimulated immunity. Compared with BCG-vaccinated nonboosted mice, we observed that infection with M.tb led to a significant increase in anti-M.tb-specific CD4 T cells in the lungs of LTK63/Ag85B-ESAT-6-boosted animals. This correlated with a significant increase in the protection against M.tb in LTK63/Ag85B-ESAT-6-boosted mice, compared with BCG-vaccinated animals. Thus, LTK63/Ag85B-ESAT-6 represents an efficient preventive vaccine against tuberculosis with a strong ability to boost prior BCG immunity.