信使核糖核酸
抗原
免疫系统
信号肽
序列(生物学)
生物
抗体
信号(编程语言)
蛋白质亚单位
翻译(生物学)
免疫学
病毒学
计算生物学
肽序列
遗传学
计算机科学
基因
程序设计语言
作者
Yupei Zhang,Songhui Zhai,Hai Huang,Shugang Qin,Min Sun,Yuting Chen,Xing Lan,Guo-Hong Li,Zhiying Huang,D. Wang,Yaoyao Luo,Wen Xiao,Hao Li,Xi He,Meiwan Chen,Xingchen Peng,Xiangrong Song
标识
DOI:10.1186/s12951-024-02488-3
摘要
Abstract The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.
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