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Evaluation of a booster tuberculosis vaccine containing mycobacterial DNA-binding protein 1 and CpG oligodeoxynucleotide G9.1 using a Guinea pig model that elicits immunity to Bacillus Calmette–Guérin
Tuberculosis ( IF 2.8 ) Pub Date : 2021-03-04 , DOI: 10.1016/j.tube.2021.102067
Jun-Ichi Maeyama 1 , Sumiko Iho 2 , Fumiko Suzuki 3 , Daisuke Hayashi 4 , Toshiko Yamamoto 4 , Toshio Yamazaki 5 , Yoshitaka Goto 6 , Yuriko Ozeki 7 , Sohkichi Matsumoto 7 , Saburo Yamamoto 4
Affiliation  

Tuberculosis is a major threat to global health and its increased incidence in adolescents as well as onset in the elderly presents a serious problem. One strategy to control tuberculosis involves taking advantage of Bacillus Calmette–Guérin's (BCG) superior effects on childhood tuberculosis. Accordingly, here we aimed to develop a booster vaccine for adults who received the BCG vaccine during early childhood. Therefore, we first devised a system to assess the efficacy of a candidate booster vaccine. Specifically, variant strain BCG-II, a minor component of BCG-Tokyo strain, which elicits weak immunity, was administered to guinea pigs. Vaccine-induced immunity and protection against Mycobacterium tuberculosis (Mtb) infection were evaluated using skin delayed-type hypersensitivity (DTH) and Mtb colony forming unit counts in organs, respectively. Candidate booster vaccine containing the mycobacterial DNA-binding protein 1 (MDP1) as antigen and CpG oligodeoxynucleotide G9.1 as adjuvant increased T-bet expression and IFN-γ production in human peripheral blood mononuclear cells. Intradermal administration of MDP1 or MDP1 and G9.1 to unimmunized guinea pigs produced DTH on MDP1-inoculated skin. Boosting BCG–II–primed guinea pigs with this protocol effectively enhanced DTH against MDP1 and protection against Mtb infection, particularly when combined with G9.1. The candidate vaccine may contribute to efforts to prevent tuberculosis.



中文翻译:


使用豚鼠模型评估含有分枝杆菌 DNA 结合蛋白 1 和 CpG 寡脱氧核苷酸 G9.1 的加强结核疫苗,该疫苗可引发对卡介苗的免疫力



结核病是对全球健康的主要威胁,其在青少年中发病率的增加以及在老年人中发病率的增加构成了一个严重的问题。控制结核病的一种策略是利用卡介苗 (BCG) 对儿童结核病的卓越疗效。因此,我们的目标是为在幼儿期接种卡介苗的成年人开发一种加强疫苗。因此,我们首先设计了一个系统来评估候选加强疫苗的功效。具体而言,将引起弱免疫力的BCG-Tokyo株的次要成分——变异株BCG-II给予豚鼠。分别使用皮肤迟发型超敏反应 (DTH) 和器官中Mtb菌落形成单位计数来评估疫苗诱导的免疫和针对结核分枝杆菌( Mtb ) 感染的保护。含有分枝杆菌 DNA 结合蛋白 1 (MDP1) 作为抗原和 CpG 寡脱氧核苷酸 G9.1 作为佐剂的候选加强疫苗可增加人外周血单核细胞中T-bet 的表达和 IFN-γ 的产生。对未免疫的豚鼠皮内施用MDP1或MDP1和G9.1在MDP1接种的皮肤上产生DTH。使用该方案增强 BCG-II 引发的豚鼠可有效增强针对 MDP1 的 DTH 和针对Mtb感染的保护,特别是与 G9.1 组合时。候选疫苗可能有助于预防结核病。

更新日期:2021-03-21
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