Development of an endotoxin detection method for mRNA vaccines based on lipid nanoparticle delivery system
10.3760/cma.j.cn112309-20250509-00142
- VernacularTitle:基于脂质纳米颗粒递送系统的mRNA疫苗的细菌内毒素检测方法研究
- Author:
Jiaru CAI
1
;
Shaoyi CHEN
;
Shuang LI
;
Juan LI
;
Yucai PENG
;
Yaru QUAN
Author Information
1. 珠海丽凡达生物技术有限公司，珠海 519000
- Publication Type:Journal Article
- Keywords:
Bacterial endotoxin;
Lipid nanoparticle;
Gel clot limit detection method;
Tachypleus amebocyte lysate;
LNP-based mRNA vaccine
- From:
Chinese Journal of Microbiology and Immunology
2025;45(11):958-964
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To develop a bacterial endotoxin detection method suitable for mRNA vaccines based on lipid nanoparticle（LNP）delivery system.Methods:The gel clot limit test outlined in the third section of the Chinese Pharmacopoeia（2020 edition）was utilized. Taking the human herpesvirus type 2 mRNA vaccine as the detection object，the optimal conditions for bacterial endotoxin detection were established by evaluating sample dilution factors，diluents，and other interfering elements. The results were validated using the recombinant C factor method. Finally，the applicability of the established method was validated through testing the respiratory syncytial virus mRNA vaccine and the shingles mRNA vaccine.Results:Increasing the sample dilution factor to 480 times with a magnesium-containing buffer and using 0.06 EU/ml tachypleus amebocyte lysate effectively mitigated the interference caused by LNP on the test results of the human herpesvirus type 2 mRNA vaccine，the respiratory syncytial virus mRNA vaccine，and the shingles mRNA vaccine. The results from recombinant C factor method and the gel clot limit method were consistent.Conclusion:A bacterial endotoxin gel clot limit detection method tailored for human herpesvirus type 2 mRNA vaccine，respiratory syncytial virus mRNA vaccine，and shingles mRNA vaccine is successfully developed based on existing protocols in the Chinese Pharmacopoeia（2020 edition）. This study offers insights for the detection of bacterial endotoxin in LNP-based biological products.
