抗体
体内
PEG比率
脾脏
医学
免疫学
病毒学
药理学
生物
财务
生物技术
经济
作者
Min Jae Yang,Zengyu Zhang,Pengpeng Jin,Kuan Jiang,Yifei Xu,Feng Pan,Kaisong Tian,Zhou Yuan,X. Liu,Jiaru Fu,Bin Wang,Huafang Yan,Changyou Zhan,Zui Zhang
标识
DOI:10.1016/j.ijpharm.2023.123695
摘要
Polyethylene glycol (PEG) plays important roles in stabilizing and lengthening circulation time of lipid nanoparticle (LNP) vaccines. Nowadays various levels of PEG antibodies have been detected in human blood, but the impact and mechanism of PEG antibodies on the in vivo performance of LNP vaccines has not been clarified thoroughly. By illustrating the distribution characteristics of PEG antibodies in human, the present study focused on the influence of PEG antibodies on the safety and efficacy of LNP-mRNA vaccine against COVID-19 in animal models. It was found that PEG antibodies led to shortened blood circulation duration, elevated accumulation and mRNA expression in liver and spleen, enhanced expression in macrophage and dendritic cells, while without affecting the production of anti-Spike protein antibodies of COVID-19 LNP vaccine. Noteworthily, PEG antibodies binding on the LNP vaccine increased probability of complement activation in animal as well as in human serum and led to lethal side effect in large dosage via intravenous injection of mice. Our data suggested that PEG antibodies in human was a risky factor of LNP-based vaccines for biosafety concerns but not efficacy.
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