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一种用于啮齿动物模型中预防呼吸道合胞病毒（RSV）感染的二价mRNA疫苗。

A bivalent mRNA vaccine against RSV infection in rodent models.

作者信息

Liu Juan, Zhao Hanqing, Wang Wenhao, Yang Binbin, Zhang Naifang, Zhang Yu, Qian Jie, Ma Qiaofang, Lu Yankun, Han Huafeng, Yang Yongsheng

机构信息

Nucleic Acid Medicine Innovation Center, Zhejiang Haichang Biotech Co., Ltd., Hangzhou, Zhejiang, China.

出版信息

Front Immunol. 2025 Mar 24;16:1542592. doi: 10.3389/fimmu.2025.1542592. eCollection 2025.

DOI:10.3389/fimmu.2025.1542592
PMID:40196112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11974254/
Abstract

Because of the higher conservation of RSV Fusion (F) protein than the glycoprotein (G) across RSV strains and serotypes, the majority of vaccine candidates targets to viral fusion protein (F) rather than glycoprotein to elicit a broader range of protective neutralizing antibodies from infection. In this study, we screened two chemically modified mRNA vaccines expressing RSV prefusion stabilized protein (preF) targeting RSV A2 and B subtypes. After immunization, the antigen-specific binding antibody, neutralizing antibody, and T cell-mediated immune response were evaluated. After challenge with live RSV A2 virus in cotton rats, the protection and safety of vaccine was further evaluated. The results showed that the mRNA vaccine candidates elicited robust antigen-specific binding antibody, neutralizing antibody responses and Th1-biased T-cell responses in both mice and cotton rats. Moreover, cotton rats vaccinated with mRNA vaccine, lung pathology and lung infectious viral loads were significantly reduced, and no vaccine enhanced respiratory disease (VERD) happened. These results collectively demonstrated that mRNA-based vaccine induced strong humoral and cellular immunity, provided outstanding protection against both RSV A2 and RSV B subtypes in rodent animals as well. Our data demonstrated that these mRNA vaccines should be further evaluated in clinical trials.

摘要

由于呼吸道合胞病毒（RSV）融合（F）蛋白在不同RSV毒株和血清型间的保守性高于糖蛋白（G），大多数候选疫苗靶向病毒融合蛋白（F）而非糖蛋白，以诱导更广泛的保护性中和抗体来预防感染。在本研究中，我们筛选了两种化学修饰的mRNA疫苗，它们表达针对RSV A2和B亚型的RSV预融合稳定蛋白（preF）。免疫后，评估了抗原特异性结合抗体、中和抗体以及T细胞介导的免疫反应。在用活的RSV A2病毒攻击棉鼠后，进一步评估了疫苗的保护作用和安全性。结果表明，候选mRNA疫苗在小鼠和棉鼠中均引发了强烈的抗原特异性结合抗体、中和抗体反应以及以Th1为主的T细胞反应。此外，接种mRNA疫苗的棉鼠，其肺部病理变化和肺部感染性病毒载量显著降低，且未发生疫苗增强性呼吸道疾病（VERD）。这些结果共同表明，基于mRNA的疫苗诱导了强大的体液免疫和细胞免疫，在啮齿动物中也对RSV A2和RSV B亚型提供了出色的保护。我们的数据表明，这些mRNA疫苗应在临床试验中进一步评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/a552ac011e07/fimmu-16-1542592-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/678426fc43a5/fimmu-16-1542592-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/a249f3ce67ca/fimmu-16-1542592-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/6373654194bb/fimmu-16-1542592-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/67148a3ebdc4/fimmu-16-1542592-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/a552ac011e07/fimmu-16-1542592-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/678426fc43a5/fimmu-16-1542592-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/a249f3ce67ca/fimmu-16-1542592-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/6373654194bb/fimmu-16-1542592-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/67148a3ebdc4/fimmu-16-1542592-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23f1/11974254/a552ac011e07/fimmu-16-1542592-g005.jpg

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本文引用的文献

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Front Immunol. 2024 Jul 26;15:1416375. doi: 10.3389/fimmu.2024.1416375. eCollection 2024.
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A new era in maternal-child health: Abrysvo's role in RSV prevention.母婴健康的新时代：Abrysvo在预防呼吸道合胞病毒方面的作用。
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RSVpreF (Abrysvo) and Nirsevimab-alip (Beyfortus) for the Prevention of Respiratory Syncytial Virus Infection.
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Humoral Immunogenicity of mRNA-1345 RSV Vaccine in Older Adults.mRNA-1345 RSV 疫苗在老年人中的体液免疫原性。
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Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons.呼吸道合胞病毒（RSV）预融合F蛋白疫苗（RSVPreF3 OA）在两个RSV流行季节对老年人的疗效和安全性
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