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一种猴痘多抗原串联二价mRNA候选疫苗可有效保护小鼠免受痘苗病毒感染。

An Mpox Multi-Antigen-Tandem Bivalent mRNA Candidate Vaccine Effectively Protects Mice Against the Vaccinia Virus.

作者信息

Zuo Jun, Wu Jiayu, Zhang Zhen, Long Jinrong, Yu Changxiao, Liao Yuqin, Zhang Hongsheng, Yang Jing

机构信息

College of Chemistry and Life Science, Beijing University of Technology, Pingleyuan 100#, District of Chaoyang, Beijing 100124, China.

Bioinformatics Center of AMMS, Beijing 100850, China.

出版信息

Vaccines (Basel). 2025 Mar 31;13(4):374. doi: 10.3390/vaccines13040374.

DOI:10.3390/vaccines13040374
PMID:40333228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12031407/
Abstract

BACKGROUND

Since the outbreak of mpox in 2022, the disease has spread rapidly worldwide and garnered significant public attention. Vaccination is regarded as an effective measure to prevent the spread of mpox. The success of the COVID-19 mRNA vaccine demonstrates that mRNA-based vaccines represent a rapid and multifunctional platform with considerable potential, and are expected to be a strategy to address mpox spread.

METHODS

In this study, we screened an mpox multi-antigen-tandem bivalent mRNA vaccine candidate: a lipid nanoparticle-encapsulated mRNA-1017 and mRNA-1995 (mRNA-3012-LNP). We then evaluated the immunogenicity of the mpox virus (MPXV) bivalent mRNA vaccine candidate and its protective efficacy against the vaccinia virus (VACV) in a mouse model.

RESULTS

Mice vaccinated with two doses of the mRNA-3012-LNP vaccine exhibited robust binding antibody responses and MPXV-specific Th-1-biased cellular immune responses in vivo. Notably, the boosted immunized mice generated potent neutralizing antibodies against the VACV, effectively protecting them from viral challenge. Additionally, serum transfer protection experiments indicated that serum from mice inoculated with mRNA-3012-LNP was effective in protecting nude mice from VACV challenge.

CONCLUSIONS

Our results suggest that the mpox bivalent mRNA candidate vaccine mRNA-3012-LNP induces strong immunogenicity and has the potential to serve as a safe and effective vaccine candidate against mpox epidemics.

摘要

背景

自2022年猴痘爆发以来,该疾病在全球迅速传播并引起了公众的广泛关注。疫苗接种被视为预防猴痘传播的有效措施。COVID-19 mRNA疫苗的成功表明,基于mRNA的疫苗是一个快速且多功能的平台,具有巨大潜力,有望成为应对猴痘传播的一种策略。

方法

在本研究中,我们筛选了一种猴痘多抗原串联二价mRNA候选疫苗:脂质纳米颗粒包裹的mRNA-1017和mRNA-1995(mRNA-3012-LNP)。然后,我们在小鼠模型中评估了该猴痘病毒(MPXV)二价mRNA候选疫苗的免疫原性及其对痘苗病毒(VACV)的保护效力。

结果

接种两剂mRNA-3012-LNP疫苗的小鼠在体内表现出强烈的结合抗体反应和MPXV特异性Th-1偏向性细胞免疫反应。值得注意的是,加强免疫的小鼠产生了针对VACV的强效中和抗体,有效保护它们免受病毒攻击。此外,血清转移保护实验表明,接种mRNA-3012-LNP的小鼠血清能有效保护裸鼠免受VACV攻击。

结论

我们的结果表明,猴痘二价mRNA候选疫苗mRNA-3012-LNP具有强大的免疫原性,有潜力成为一种安全有效的抗猴痘流行疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/2789e5885ea9/vaccines-13-00374-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/eaa67661a3e4/vaccines-13-00374-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/429a9f615b1a/vaccines-13-00374-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/52fcc0aa6d90/vaccines-13-00374-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/07fe6710ae52/vaccines-13-00374-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/2789e5885ea9/vaccines-13-00374-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/eaa67661a3e4/vaccines-13-00374-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/429a9f615b1a/vaccines-13-00374-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/52fcc0aa6d90/vaccines-13-00374-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/07fe6710ae52/vaccines-13-00374-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/523e/12031407/2789e5885ea9/vaccines-13-00374-g005.jpg

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本文引用的文献

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Comparison of protection against mpox following mRNA or modified vaccinia Ankara vaccination in nonhuman primates.mRNA 或改良安卡拉痘苗病毒疫苗对非人灵长类动物预防猴痘的效果比较。
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A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease.一种多价信使核糖核酸猴痘病毒疫苗(BNT166)可保护小鼠和猕猴免受正痘病毒疾病侵害。
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Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.I 型分支相关猴痘病例与性接触相关,刚果民主共和国。
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Dendritic Cell-Mimicking Nanoparticles Promote mRNA Delivery to Lymphoid Organs.树突状细胞模拟纳米颗粒促进 mRNA 递送至淋巴器官。
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An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge.一种天花病毒 mRNA-脂质纳米颗粒疫苗可预防致死性正痘病毒攻击。
Sci Transl Med. 2023 Oct 4;15(716):eadg3540. doi: 10.1126/scitranslmed.adg3540.
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Viruses. 2023 Jul 28;15(8):1649. doi: 10.3390/v15081649.
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Monkeypox virus quadrivalent mRNA vaccine induces immune response and protects against vaccinia virus.猴痘病毒四价 mRNA 疫苗可诱导免疫应答并预防牛痘病毒。
Signal Transduct Target Ther. 2023 Apr 28;8(1):172. doi: 10.1038/s41392-023-01432-5.