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反PEG抗体对mRNA载脂纳米粒子免疫反应的影响
Daiki Omata1, Eigo Kawahara2,3, Lisa Munakata1
1Laboratory of Drug and Gene Delivery Research, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo 173-8605, Japan.
Molecular pharmaceutics
|September 26, 2024
概括
脂质纳米颗粒封装的mRNA疫苗可以触发抗聚乙烯糖醇 (PEG) 抗体. 这些抗体对疫苗没有显著的影响.
科学领域:
- 免疫学 免疫学 免疫学
- 疫苗学 疫苗学 疫苗学
- 纳米技术 纳米技术
背景情况:
- 脂质纳米粒子封装mRNA (mRNA-LNP) 疫苗对于抗击COVID-19至关重要.
- 这些疫苗利用PEG结合脂质,可以引起抗PEG抗体反应.
- 以前的研究表明,抗PEG抗体不会阻碍中和抗体的产生,但它们的整体影响尚不清楚.
研究的目的:
- 研究抗PEG抗体对mRNA-LNP疫苗诱导的抗原特异性免疫反应的影响.
- 用模型抗原来确定是否存在的抗PEG抗体会影响mRNA-LNP疫苗接种的疗效.
主要方法:
- 作为模型抗原系统的卵蛋白 (OVA) mRNA载荷LNP (mRNA-OVA-LNP) 的制备.
- 在小鼠中通过使用PEG修饰脂质体进行预处理,诱导抗PEG抗体.
- 肌肉内注射 (I.M.) 的方法 在小鼠中注射mRNA-OVA-LNP,并评估免疫反应.
主要成果:
- 在mRNA-LNP接种疫苗后,抗PEG抗体没有改变蛋白质表达,细胞因子诱导或细胞免疫反应.
- 在存在抗PEG抗体时,观察到抗原特异性抗体诱导的轻微增加.
- 重复的mRNA-LNP注射导致了抗PEG IgM和抗PEG IgG抗体的产生.
结论:
- mRNA-LNP诱导抗PEG抗体,但这种反应不会显著损害疫苗主导抗原特异性免疫反应的能力.
- 这些发现表明,mRNA-LNP疫苗产生的抗PEG抗体对疫苗的原发性免疫功能的影响很小.
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