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mRNA 疫苗高效信号序列增强抗原表达，扩大免疫保护以抵抗病毒感染。

Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection.

机构信息

Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.

出版信息

J Nanobiotechnology. 2024 May 28;22(1):295. doi: 10.1186/s12951-024-02488-3.

DOI:10.1186/s12951-024-02488-3
PMID:38807131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11134928/
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.

摘要

信号序列通过影响抗原翻译，在针对病毒大流行的 mRNA 疫苗的疗效中发挥着关键作用。然而，对于比较和分析具体的作用机制，目前的研究还很有限。在这项研究中，我们采用了一种新的方法，通过替换 mRNA 抗原的信号序列来增强其免疫反应。计算模拟表明，不同的信号肽与信号识别颗粒（SRP）54M 亚基的结合能力不同，这与抗原翻译效率呈正相关。我们的数据表明，tPA 和 IL-6 修饰的受体结合域（RBD）mRNA 疫苗的信号序列依次导致更高的抗原表达，并引发针对 SARS-CoV-2 的更强大的体液和细胞免疫保护，与原始信号序列相比。通过强调信号序列的重要性，这项研究为信号序列-抗原设计的持续修改提供了一个基础和安全的方法，旨在优化 mRNA 疫苗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/bc58fbbf4cb7/12951_2024_2488_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/7368540c963f/12951_2024_2488_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/f8d591fcff24/12951_2024_2488_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/39027f035582/12951_2024_2488_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/b8748cb76c3a/12951_2024_2488_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/e55f3f583152/12951_2024_2488_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/bc58fbbf4cb7/12951_2024_2488_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/7368540c963f/12951_2024_2488_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/f8d591fcff24/12951_2024_2488_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/39027f035582/12951_2024_2488_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/b8748cb76c3a/12951_2024_2488_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/e55f3f583152/12951_2024_2488_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5e/11134928/bc58fbbf4cb7/12951_2024_2488_Fig6_HTML.jpg

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