效价
2019年冠状病毒病(COVID-19)
翻译(生物学)
中和抗体
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
抗体
疫苗效力
病毒学
信使核糖核酸
生物
基因
接种疫苗
医学
免疫学
生物化学
传染病(医学专业)
疾病
病理
作者
Kepan Chen,Na Fan,Hai Huang,Xin Jiang,Shugang Qin,Wen Xiao,Qian Zheng,Yupei Zhang,Xing Duan,Zeyi Qin,Yongmei Liu,Jun Zeng,Yuquan Wei,Xiangrong Song
标识
DOI:10.1002/adfm.202204692
摘要
SARS-CoV-2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS-CoV-2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T-LNPs. Leading 4N4T-LNPs exhibit much higher mRNA translation efficiency than the approved SM-102-LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full-length S protein of the SARS-CoV-2 variant is synthesized and loaded in 4N4T-LNPs. The obtained 4N4T-DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS-CoV-2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD-specific IgG titers and neutralizing antibody titers than SM-102-based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine-induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T-DS mRNA vaccines also induce strong Th1-skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS-CoV-2 variants.
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