一种多价mRNA疫苗在猴痘病毒感染的小鼠模型中引发了强烈的免疫反应并提供了保护。

A multivalent mRNA vaccine elicits robust immune responses and confers protection in a murine model of monkeypox virus infection.

作者信息

Li Yansheng, Cheng Lin, Jiang Lixu, Li Zhuohuan, Rao Jing, Wu Tong, Zhang Fangyan, Xie Baocai, He Yu, Wang Lianrong, Zhang Zheng, Chen Shi

机构信息

Department of Critical Care Medicine, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Guangdong Provincial Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Institute of Translational Medicine, Shenzhen University Medical School, Shenzhen Second People' Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.

出版信息

Nat Commun. 2025 Aug 9;16(1):7373. doi: 10.1038/s41467-025-61699-w.

DOI:10.1038/s41467-025-61699-w

PMID:40783493

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12335498/

Abstract

Monkeypox virus (MPXV) has re-emerged globally since May 2022, posing a significant public health threat. To address this, we develop two multivalent mRNA vaccine candidates-AAL, encoding three MPXV antigens, and AALI, which combines AAL with an immune-enhancing IFN-α protein. Both vaccines are delivered via mannose-modified lipid nanoparticles to target dendritic cells. Here we show that these vaccines elicit strong antibody responses against vaccinia virus and multiple MPXV clades, induce robust memory B-cell and T-cell responses, and promote dendritic cell maturation. In mouse challenge models, both vaccines provide protection against clade IIb MPXV and vaccinia virus, significantly reducing viral loads and preventing lung damage. Immune profiling reveals enhanced B- and T-cell receptor diversity and distinct CDR3 motifs post-vaccination. These findings demonstrate the potential of using mRNA-based multivalent vaccines as an effective strategy for preventing mpox and related Orthopoxvirus infections.

摘要

自2022年5月以来，猴痘病毒（MPXV）在全球范围内再次出现，对公共卫生构成重大威胁。为应对这一情况，我们研发了两种多价mRNA候选疫苗——AAL，编码三种MPXV抗原；以及AALI，它将AAL与一种免疫增强型IFN-α蛋白相结合。两种疫苗均通过甘露糖修饰的脂质纳米颗粒递送，以靶向树突状细胞。在此我们表明，这些疫苗可引发针对痘苗病毒和多个MPXV分支的强烈抗体反应，诱导强大的记忆B细胞和T细胞反应，并促进树突状细胞成熟。在小鼠攻毒模型中，两种疫苗均能提供针对IIb分支MPXV和痘苗病毒的保护，显著降低病毒载量并预防肺部损伤。免疫分析显示，接种疫苗后B细胞和T细胞受体多样性增强，且互补决定区（CDR3）基序不同。这些发现证明了使用基于mRNA的多价疫苗作为预防猴痘及相关正痘病毒感染的有效策略的潜力。