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将免疫刺激性脂质纳入脂质纳米颗粒:探索表达和免疫反应

Maria Evdokimou¹, Hakam Alaqabani², Muattaz Hussain¹

¹Strathclyde Institute of Pharmacy and Biomedical Sciences, 161 Cathedral Street, University of Strathclyde, Glasgow G4 0RE, UK.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

|February 27, 2026

概括

研究人员探索了为mRNA疫苗添加二甲基二氧化十三胺 (DDAB) 到脂质纳米粒子 (LNPs). 虽然DDAB在体外改善了mRNA表达,但在小鼠体内减少了表达和免疫性,对疫苗开发没有任何好处.

科学领域:

生物技术是生物技术.
疫苗开发疫苗开发
纳米医学是一种纳米医学.

背景情况:

脂质纳米颗粒 (LNP) 对于mRNA疫苗的输送至关重要.
了解脂质组成对LNP免疫性的影响至关重要.
甲基二甲酸十甲基胺 (DDAB) 是一种带有潜在免疫刺激性质的阴性脂质.

研究的目的:

调查将DDAB纳入SM-102 LNP对mRNA疫苗输送和免疫性的影响.
评估不同的DDAB比率如何影响LNP的物理化学性质和生物性能.
为了确定DDAB是否增强细胞吸收,抗原表达和免疫激活,用于疫苗应用.

主要方法:

配制的LNP具有不同比例的SM-102和DDAB (0-50mol%),以及DSPC,胆固醇和DMG-PEG2000.
用于粒子大小,PDI,泽塔潜力和mRNA封装效率的特征配方.
在肌肉内注射后评估了HEK293细胞中的体外mRNA表达和体内光酶表达.
在免疫接种后的小鼠中评估了抗体反应.

主要成果:

增加DDAB含量增加了粒子大小,但保持了低PDI,中性表面电荷和高mRNA封装.
DDAB的整合改变了LNP pKa,表明在更高的百分比下,阴性电荷占主导地位增加了.
在体外,10%的DDAB LNP显示mRNA表达增加了六倍;然而,体内表达显著减少.
较低的DDAB水平 (10-30%) 不会影响抗体反应,而较高的水平 (≥40%) 会降低免疫性.

结论:

将DDAB纳入SM-102 LNPs并没有提高mRNA疫苗在体内的性能或免疫性.
较高的DDAB度对体内表达和整体免疫反应产生了负面影响.
该研究表明,根据目前的发现,在mRNA疫苗开发中使用DDAB修改的SM-102 LNP没有任何优势.

关键词:

抗体反应对抗体反应免疫性免疫性免疫性免疫刺激性脂类可离子化的脂质离子化脂质脂质纳米颗粒的使用方法转化转化转化转化提供mRNA的交付.混合的阴离子 LNP.

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