An alphavirus vaccine development utilizing RNA replication-defective strategy.

IF 12 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-09-02 DOI:10.1016/j.ymthe.2025.08.051

Zherui Zhang, Jie Huang, Zhenye Li, Chenglin Deng, Hongqing Zhang, Bo Zhang, Yanan Zhang

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引用次数: 0

Abstract

Alphaviruses are arthropod-borne viruses that cause widespread disease. However, many pathogenic alphaviruses are classified as risk group 3 human pathogens, which hampers the development of vaccines and therapeutic agents targeting alphavirus infections. In this study, we developed an RNA replication-defective Venezuelan equine encephalitis virus that has a complete nsP4 gene deletion (VEEV-ΔnsP4). A BHK cell line expressing nsP4 (BHK_nsP4) was selected for trans-complementation to support the replication cycle of VEEV-ΔnsP4. The VEEV-ΔnsP4 replicates only in BHK_nsP4 cells and is immunologically similar to its parental wild type. Significantly, VEEV-ΔnsP4 is highly attenuated and a single dose immunization can protect mice from a lethal challenge. Furthermore, the RNA replication-defective vaccine strategy has been successfully employed for Chikungunya virus (CHIKV), Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV). Overall, our study highlights the potential of the nsP4 trans-complementation system as a safe and effective platform for alphavirus vaccines development.

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利用RNA复制缺陷策略研制甲病毒疫苗。

甲病毒是节肢动物传播的病毒，可引起广泛的疾病。然而，许多致病性甲病毒被归类为风险组3的人类病原体，这阻碍了针对甲病毒感染的疫苗和治疗剂的开发。在这项研究中，我们开发了一种RNA复制缺陷委内瑞拉马脑炎病毒，该病毒具有完全的nsP4基因缺失（VEEV-△nsP4）。选择表达nsP4的BHK细胞株（BHKnsP4）进行反式互补，以支持VEEV-△nsP4的复制周期。VEEV-△nsP4仅在BHKnsP4细胞中复制，免疫学上与其亲本野生型相似。值得注意的是，VEEV-△nsP4是高度减毒的，单次免疫可以保护小鼠免受致命的攻击。此外，RNA复制缺陷疫苗策略已成功应用于基孔肯雅病毒（CHIKV）、西部马脑炎病毒（WEEV）和东部马脑炎病毒（EEEV）。总之，我们的研究强调了nsP4反式互补系统作为甲病毒疫苗开发安全有效平台的潜力。

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

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.