Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers

IF 26.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Nature Biomedical Engineering Pub Date : 2024-05-07 DOI:10.1038/s41551-024-01208-4

Di Yin, Yiye Zhong, Sikai Ling, Sicong Lu, Xiaoyuan Wang, Zhuofan Jiang, Jie Wang, Yao Dai, Xiaolong Tian, Qijing Huang, Xingbo Wang, Junsong Chen, Ziying Li, Yang Li, Zhijue Xu, Hewei Jiang, Yuqing Wu, Yi Shi, Quanjun Wang, Jianjiang Xu, Wei Hong, Heng Xue, Hang Yang, Yan Zhang, Lintai Da, Ze-guang Han, Sheng-ce Tao, Ruijiao Dong, Tianlei Ying, Jiaxu Hong, Yujia Cai

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Abstract

Messenger RNA vaccines lack specificity for dendritic cells (DCs)—the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid–nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

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树突状细胞靶向病毒样颗粒作为强效 mRNA 疫苗载体

信使 RNA 疫苗对树突状细胞（DC）缺乏特异性，而树突状细胞是最有效的抗原递呈细胞。在这里，我们报告了一种DC靶向病毒样颗粒的设计和性能，这种病毒样颗粒伪型为可识别DC表面蛋白的工程化辛比斯病毒糖蛋白，并包装有编码严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）穗状病毒蛋白或单纯疱疹病毒1糖蛋白B和D的mRNA。在小鼠足垫中注射直流电靶向 SARS-CoV-2 mRNA 疫苗后，小鼠的抗原特异性免疫球蛋白-G 滴度和细胞免疫反应显著高于非靶向病毒样颗粒和脂质纳米颗粒制剂。这些疫苗还能保护小鼠免受 SARS-CoV-2 或单纯疱疹病毒 1 的感染。被直流细胞优先摄取的病毒样颗粒可能会促进强效预防性和治疗性疫苗的开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Biomedical Engineering Medicine-Medicine (miscellaneous)

CiteScore

45.30

自引率

1.10%

发文量

138

期刊介绍： Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.