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增加了针对结核病的疫苗疗效,其中一个重组BCG过度表达了STING激动剂循环二-AMP

Dhiraj K Singh¹, Peter Um², Garima Arora¹

¹Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.

bioRxiv : the preprint server for biology

|August 12, 2025

概括

一种经过修改的Bacillus Calmette Guérin (BCG) 疫苗,BCG-STING,在非人类灵长类模型中显著增强了对结核病 (TB) 的保护. 这种改进的候选疫苗利用现有的BCG平台,以更好地预防结核病和免疫反应.

科学领域:

免疫学免疫学免疫学
疫苗学疫苗学疫苗学
微生物学微生物学

背景情况:

结核病 (TB) 是全球主要的传染性死亡原因.
细菌卡尔梅特·盖林 (BCG) 是唯一获得许可的结核病疫苗,但在成年人中有效性有限.
修改后的BCG (modBCG) 疫苗可以提高有效性,同时保持BCG的安全性.

研究的目的:

评估BCG-STING,一种过度表达disA基因的重组BCG,作为一种新型抗结核病疫苗候选人.
为了比较BCG-STING对非人类灵长类结核病模型中的父母BCG-WT菌株的疗效.

主要方法:

BCG-STING和BCG-WT是通过皮内注射给 rhesus 的.
这些动物被挑战了毒性Mycobacterium结核病 (Mtb).
评估了mtb殖民地形成单元 (CFU),肺病理和T细胞反应.

主要成果:

BCG-STING耐受性良好,并导致支气管支气管泡泡洗样本中的Mtb CFU数量降低.
接种BCG-STING疫苗的动物显示MTB肺CFU显著减少,肺叶更加无菌.
增强的保护与高抗原特异性CD4+和CD8+T细胞反应相关.

结论:

通过disA修改BCG以过度表达一种STING激动剂 (循环di-AMP),可以提高疫苗对结核病的疗效.
在非人类灵长类动物模型中,BCG-STING证明了更好的保护和细胞介导免疫力.
这种方法为开发更有效的结核病疫苗提供了一个有希望的战略.

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