Synergistic effect of bacillus Calmette Guerin and a tuberculosis subunit vaccine in cationic liposomes: Increased immunogenicity and protection
Synergistic effect of bacillus Calmette Guerin and a tuberculosis subunit vaccine in cationic liposomes: Increased immunogenicity and protection
复制标题
DOI：
10.4049/jimmunol.178.6.3721
复制
发表时间：
2007-03-15
影响因子：
4.4
通讯作者：
Andersen, Peter
中科院分区：
文献类型：
--
作者：
Dietrich, Jes;Billeskov, Rolf;Andersen, Peter
在目前的工作中，我们评估了一种新的结核病疫苗的基础上的组合的牛分枝杆菌卡介苗（BCG）疫苗和亚单位疫苗组成的蛋白质Ag 85 B抗ESAT-6的方法。我们证明，除了它的疫苗效力BCG是一种免疫调节剂，可以增强Th 1免疫应答比众所周知的佐剂单磷酰脂质A，导致增强识别的亚单位疫苗Ag 85 B-ESAT-6。重要的是，向疫苗中加入载体，如阳离子脂质体二甲基双十八烷基溴化铵（DDA），显著增加了BCG的增强作用。BCG和Ag 85 B-ESAT-6/脂质体之间的这种协同效应需要将所有疫苗组分引流至相同的淋巴结，但不需要直接混合组分，因此当BCG和Ag 85 B-ESAT-6/脂质体在引流至相同淋巴结的部位作为单独注射给药时也观察到。由BCG和脂质体中的亚单位（并排注射）组成的所得优化疫苗方案随后用常规佐剂中的亚单位加强导致与单独BCG相比高达7倍的保护效力的令人印象深刻的增加，并且与通过亚单位疫苗加强的未增强的BCG相比增加3倍。因此，这些研究提出了一种免疫策略，其中将新型TB亚单位疫苗作为儿童疫苗接种计划的一部分与新生儿中的BCG一起施用，然后进行亚单位加强。
In the present work, we evaluated a new TB vaccine approach based on a combination of the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine and a subunit vaccine consisting of the proteins Ag85B anti ESAT-6. We demonstrate that in addition to its vaccine efficacy BCG is an immune modulator that can potentiate a Th1 immune response better than the well-known adjuvant mono phosphoryl lipid A, leading to enhanced recognition of the subunit vaccine Ag85B-ESAT-6. Importantly, adding a vehicle to the vaccine, such as the cationic liposome dimethyl dioctadecyl ammonium bromide (DDA), significantly increased the potentiating effect of BCG. This synergistic effect between BCG and Ag85B-ESAT-6/liposome required drainage to the same lymph node of all vaccine components but did not require direct mixing of the components and was therefore also observed when BCG and Ag85B-ESAT-6/liposome were given as separate injections at sites draining to the same lymph node. The resulting optimized vaccine protocol consisting of BCG and subunit in liposomes (injected side by side) followed by boosting with the subunit in conventional adjuvant resulted in an impressive increase in the protective efficacy of up to 7-fold compared with BCG alone and 3-fold compared with unaugmented BCG boosted by the subunit vaccine. Thus, these studies suggest an immunization strategy where a novel TB subunit vaccine is administered as part of the child vaccination program together with BCG in neonates and followed by subunit boosting.