信使核糖核酸
CD8型
免疫系统
抗体
脾脏
2019年冠状病毒病(COVID-19)
化学
受体
生物
病毒学
生物化学
医学
免疫学
基因
疾病
内科学
传染病(医学专业)
作者
Ke Huang,Na Li,Yingwen Li,Jiafeng Zhu,Qianyi Fan,Jiali Yang,Yinjia Gao,Yupin Liu,Qiangbo Hou,Shufeng Gao,Ke Wei,Chao Deng,Chijian Zuo,Zhenhua Sun
标识
DOI:10.1101/2022.05.12.491597
摘要
ABSTRACT mRNA vaccines have emerged as a most promising and potent platform in the fight against various diseases including the COVID-19 pandemic. However, the intrinsic instability, varying side effects associated with the delivery systems, and continuous emergence of virus variants highlight the urgent need for the development of stable, safe and efficacious mRNA vaccines. In this study, by screening a panel of proprietary biodegradable ionizable lipidoids, we reported on a novel mRNA vaccine (cmRNA-1130) formed from a biodegradable lipidoid with eight ester bonds in the branched tail (AX4) and synthetic circular mRNA (cmRNA) encoding the trimeric Delta receptor binding domain (RBD) of SARS-CoV-2 spike protein for the induction of robust immune activation. The AX4-based lipid nanoparticles (AX4-LNP) revealed much faster elimination rate from liver and spleen in comparison with commercialized MC3-based LNP (MC3-LNP) and afforded normal level of alanine transferase (ALT), aspartate aminotransferase (AST), and creatinine (CRE) in BALB/c mice. Following intramuscular (IM) administration in BALB/c mice, cmRNA-1130 elicited potent and sustained neutralizing antibodies, RBD-specific CD4 + and CD8 + T effector memory cells (Tem), and Th1-biased T cell activations. cmRNA-1130 vaccine showed excellent stability against 6-month storage at 4 □ and freezing-thawing cycles. In brief, our study highlights mRNA vaccines based on cmRNA and biodegradable AX4 lipids hold great potential as superb therapeutic platforms for the treatment of varying diseases.
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