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一种BCG杀死开关菌株可以保护小鼠和非人类灵长类动物的结核菌,并提高了安全性和免疫性

Alexander A Smith^1,2, Hongwei Su^3,4, Joshua Wallach³

¹Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Nature microbiology

|January 10, 2025

概括

一个小说一个小说

科学领域:

微生物学微生物学
免疫学免疫学免疫学
疫苗学疫苗学疫苗学

背景情况:

结核病 (TB) 仍然是全球健康威胁,需要改进疫苗.
静脉注射 (IV) 输入静脉注射 (IV) 输入静脉注射提供活体减弱的Bacillus Calmette-Guérin (BCG) 是有希望的,但也引发了安全问题.
目前的BCG疫苗在有效性和安全性方面存在局限性.

研究的目的:

开发一种基因工程"杀死开关"BCG疫苗,以提高安全性和有效性.
在临床前模型中评估改性BCG菌株的安全性和免疫性.
评估工程BCG对Mycobacterium结核病 (Mtb) 的保护功效的挑战.

主要方法:

对BCG进行基因工程以表达菌素溶酶,从而产生可诱导 (BCG-TetON-DL) 和可抑制 (BCG-TetOFF-DL) 菌株.
在体外和体内评估BCG活性的存在和缺乏四环素.
在接种疫苗后,对小鼠和的免疫反应和对Mtb的保护进行评估.

主要成果:

素表达有效地杀死了工程BCG在体外,巨细胞,免疫能力和免疫功能低下的小鼠.
在中给予BCG-TetOFF-DL,随后进行四环素禁用,减少细菌负载和增强肺CD4T细胞反应.
该BCG-TetOFF-DL菌株在中提供了强大的防治Mtb挑战的保护,在8只动物中,有6只动物获得了绝育免疫力.

结论:

一种四环素控制的"杀死开关"BCG疫苗 (BCG-TetOFF-DL) 通过使细菌清除,提高了安全性.
与野生型BCG相比,这种工程化BCG引起强烈的免疫反应,并提供对Mtb感染的优越保护.
杀死开关疫苗的开发代表了结核疫苗接种战略的重大进展.

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