Effectiveness of a broad-spectrum bivalent mRNA vaccine against SARS-CoV-2 variants in preclinical studies.

IF 8.4 2区医学 Q1 IMMUNOLOGY

Emerging Microbes & Infections Pub Date : 2024-12-01 Epub Date: 2024-02-29 DOI:10.1080/22221751.2024.2321994

Jing Lu, Shudan Tan, Hao Gu, Kunpeng Liu, Wei Huang, Zhaoli Yu, Guoliang Lu, Zihan Wu, Xiaobo Gao, Jinghua Zhao, Zongting Yao, Feng Yi, Yantao Yang, Hu Wang, Xue Hu, Mingqing Lu, Wei Li, Hui Zhou, Hang Yu, Chao Shan, Jinzhong Lin

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引用次数: 0

Abstract

Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.

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广谱双价 mRNA 疫苗在临床前研究中对 SARS-CoV-2 变种的有效性。

利用改良信使核糖核酸（mRNA）技术制成的疫苗已显示出对人类 SARS-CoV-2 的强大保护效力。随着病毒在人类和非人类宿主中的不断进化，疫苗的性能仍有可能受到具有强大免疫逃逸能力的新变种的影响。在此，我们介绍了新型二价 mRNA 疫苗 RQ3025 在动物模型中安全性和有效性的临床前研究。该疫苗的 mRNA 序列设计纳入了 SARS-CoV-2 穗状病毒蛋白上的常见突变，这些突变是在不同变种的进化过程中发现的。在小鼠（BALB/c 和 K18-hACE2）、仓鼠和大鼠体内注射 RQ3025 后，可诱导出针对多种变异体的广谱、高滴度中和抗体，显示出与单价 mRNA 疫苗相比的优势。接种了 RQ3025 疫苗的大鼠也能有效抵御几种新出现的变种。对 BALB/c 小鼠脾细胞衍生细胞因子的分析表明，RQ3025 诱导了 Th1 偏向的细胞免疫反应。注射高剂量 RQ3025 后，对大鼠多个器官的组织学分析表明，没有病理变化的证据。这项研究证明了 RQ3025 作为一种广谱疫苗在动物模型中对 SARS-CoV-2 变体的安全性和有效性，并为其将来可能的临床应用奠定了基础。

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

Emerging Microbes & Infections IMMUNOLOGY-MICROBIOLOGY

CiteScore

26.20

自引率

2.30%

发文量

276

审稿时长

20 weeks

期刊介绍： Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses. The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries. This journal addresses topics of critical biological and clinical importance, including but not limited to: - Epidemic surveillance - Clinical manifestations - Diagnosis and management - Cellular and molecular pathogenesis - Innate and acquired immune responses between emerging microbes and their hosts - Drug discovery - Vaccine development research Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.