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广谱二价 mRNA 疫苗在临床前研究中对 SARS-CoV-2 变异株的有效性。

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

机构信息

State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People's Republic of China.

出版信息

Emerg Microbes Infect. 2024 Dec;13(1):2321994. doi: 10.1080/22221751.2024.2321994. Epub 2024 Feb 29.

DOI:10.1080/22221751.2024.2321994
PMID:38377136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10906132/
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.

摘要

利用修饰信使 RNA（mRNA）技术的疫苗已在人类中显示出针对 SARS-CoV-2 的强大保护效力。随着病毒在人类和非人类宿主中不断进化，仍然存在风险，即新的具有强大免疫逃逸能力的变体可能会影响疫苗的性能。在这里，我们介绍了一种新型二价 mRNA 疫苗 RQ3025 的临床前特征，以评估其在动物模型中的安全性和有效性。该疫苗的 mRNA 序列设计为包含在不同变体的进化过程中发现的 SARS-CoV-2 刺突蛋白上的常见突变。在注射 RQ3025 后，小鼠（BALB/c 和 K18-hACE2）、仓鼠和大鼠中诱导了针对多种变体的广谱、高滴度中和抗体，这表明其优于单价 mRNA 疫苗。在预防几种新出现的变体方面的有效性在接种 RQ3025 的大鼠中也很明显。对 BALB/c 小鼠来源的脾细胞细胞因子的分析表明，RQ3025 诱导了 Th1 偏向的细胞免疫反应。对高剂量 RQ3025 注射后大鼠的多个器官进行组织学分析显示没有病理变化的证据。这项研究证明了 RQ3025 在动物模型中作为针对 SARS-CoV-2 变体的广谱疫苗的安全性和有效性，并为其未来的潜在临床应用奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb5a/10906132/4c88d18273d1/TEMI_A_2321994_F0007_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb5a/10906132/1ec4fc056119/TEMI_A_2321994_F0001_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb5a/10906132/f85377a24dda/TEMI_A_2321994_F0005_OC.jpg
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