An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2024-07-31 DOI:10.1016/j.antiviral.2024.105974

Entao Li , Qizan Gong , Jiachen Zhang , Xiaoping Guo , Wenyu Xie , Da Chen , Yanqiong Shen , Dongxiang Hong , Zhihao Li , Qianqian Wang , Chao Wang , Yucai Wang , Sandra Chiu

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引用次数: 0

Abstract

The outbreak of 2022 monkeypox virus (MPXV) infection in nonendemic regions is a global public health concern. A highly effective and safe MPXV vaccine that is available to the general public is urgently needed to control the mpox pandemic. Here, we developed a multivalent mRNA vaccine candidate, MPXV-1103, which expresses the full-length B6, A35, A29 and M1 proteins with three flexible linkers (G₄S₁)₃ in a single sequence. Compared with the monovalent MPXV mRNA vaccine candidates or the quadrivalent mRNA vaccine from mixtures of the four monovalent MPXV mRNA vaccines, MPXV-1103 elicits a robust humoral response and an MPXV-specific T-cell response and protects mice from lethal vaccinia virus (VACV) challenge, with no live virus detected in the nasal or lungs even at dosages as low as 1 μg. Furthermore, analysis of complete blood counts and photomicrographs of tissue from the main organs of mice vaccinated with MPXV-1103 at doses of 5 μg and 20 μg revealed that two doses of MPXV-1103 did not cause any observable pathological changes in the mice. Collectively, our results suggest that MPXV-1103, with features of high efficacy, safety and a simplified manufacturing process, is a promising vaccine candidate for defending against MPXV infection.

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一种 mpox 四价 mRNA 疫苗能保护小鼠免受致命的疫苗病毒挑战。

2022 年猴痘病毒 (MPXV) 感染在非流行地区的爆发是一个全球性的公共卫生问题。为控制猴痘病毒的大流行，迫切需要一种高效、安全且可供大众使用的猴痘病毒疫苗。在此，我们开发了一种多价 mRNA 候选疫苗 MPXV-1103，它在单一序列中表达了全长的 B6、A35、A29 和 M1 蛋白以及三个柔性连接体（G4S1）3。与单价 MPXV mRNA 候选疫苗或由四种单价 MPXV mRNA 疫苗的混合物制成的四价 mRNA 疫苗相比，MPXV-1103 能引起强大的体液反应和 MPXV 特异性 T 细胞反应，并保护小鼠免受致命性疫苗病毒 (VACV) 的挑战，即使剂量低至 1 μg，鼻腔或肺部也检测不到活病毒。此外，对接种 5 μg 和 20 μg 剂量 MPXV-1103 的小鼠进行的全血细胞计数和主要器官组织显微照片分析表明，两种剂量的 MPXV-1103 均未对小鼠造成任何可观察到的病理变化。总之，我们的研究结果表明，MPXV-1103 具有高效、安全和生产工艺简化等特点，是一种很有希望的用于预防 MPXV 感染的候选疫苗。

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

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.