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由肺向的mRNA-LNP诱导的过度肺炎抑制了针对结核病的疫苗

Liyan Li¹, Zeyu Yang¹, Hong Liu^2,3

¹School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou 510275, China.

ACS applied materials & interfaces

|May 16, 2025

概括

针对肺部的mRNA疫苗编码Ag85B和ESAT6,有或没有单酸脂A (MPLA),诱导T细胞反应,但引起肺炎. 辅助疫苗加剧了炎症,并削弱了对结核病 (TB) 的保护.

科学领域:

疫苗学疫苗学疫苗学
免疫学免疫学免疫学
传染性疾病传染性疾病

背景情况:

开发一种有效的结核病 (TB) 疫苗是具有挑战性的,因为结核菌 (Mtb) 的复杂性.
传递 RNA (mRNA) 疫苗提供了一个灵活的平台来传递多个抗原,显示了结核病疫苗开发的前景.

研究的目的:

设计和评估一个针对肺部的mRNA疫苗 (LNP_肺-mRNA_A-E) 编码Ag85B和ESAT6用于结核病.
评估单脂A (MPLA) 作为辅助剂对mRNA疫苗的疗效和安全性的影响.

主要方法:

构建的脂质纳米粒子 (LNP) 针对肺部,封装编码Ag85B和ESAT6的mRNA (LNP<肺>-mRNA).
与LNP-mRNA疫苗 (LNP_肺-mRNA_A-E-MPLA) 共同配制的MPLA,以创建一个辅助剂配方.
在小鼠模型中评估免疫反应 (CD4+ T细胞,IFN-γ,TNF-α,IL-2) 和对Mtb挑战的保护,并对肺组织进行组织学分析.

主要成果:

无论是LNP_肺-mRNA_A-E还是LNP_肺-mRNA_A-E-MPLA都诱导了强大的CD4+T细胞反应,并增加了IFN-γ,TNF-α和IL-2的局部产生.
添加MPLA增强了免疫性,但没有改善对Mtb挑战的保护;疫苗配方也没有增强BCG原始免疫力.
LNP_肺-mRNA_A-E-MPLA诱导了显著的肺炎,组织损伤和IL-6,IL-1β和MCP-1的水平升高,MPLA加剧了这些影响.

结论:

针对肺部的mRNA疫苗,特别是当添加MPLA时,可以诱导有害的肺炎并降低对结核病的保护性免疫力.
缓解慢性肺炎的策略对于成功开发针对肺部的mRNA疫苗来治疗传染病至关重要.

关键词:

细胞免疫力细胞免疫力这是一种炎症炎症炎症炎症.肺部向的LNP是肺部的目标.这是mRNA疫苗.结核病是一种肺结核病.

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