文献类型：期刊文献

英文题名：Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity

作者：Zhang, Niubing[1,6,7];Cheng, Xiang[1,8];Zhu, Yilong[2,5];Mo, Ouyang[3,8];Yu, Huiqing[3];Zhu, Liqi[3,8];Zhang, Juan[3,8];Kuang, Linlin[3];Gao, Ying[3,8];Cao, Ruiyuan[4];Liang, Xiaozhen[3,8];Wang, Haikun[3,8];Li, Honglin[6,7];Li, Song[4];Zhong, Wu[4];Li, Xuan[1,8];Li, Xiao[2];Hao, Pei[3,8]

机构：[1]Chinese Acad Sci, Inst Plant Physiol & Ecol, CAS Ctr Excellence Mol Plant Sci, Key Lab Synthet Biol, Shanghai 200032, Peoples R China;[2]Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China;[3]Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai 200031, Peoples R China;[4]Beijing Inst Pharmacol & Toxicol, Natl Engn Res Ctr Emergency Drug, Beijing 100850, Peoples R China;[5]Changchun Univ Chinese Med, Academicians Workstat Jilin Prov, Changchun 130117, Peoples R China;[6]East China Univ Sci & Technol, Shanghai 200237, Peoples R China;[7]Lingang Lab, Shanghai 200031, Peoples R China;[8]Univ Chinese Acad Sci, Beijing 100049, Peoples R China

年份：2023

卷号：66

期号：10

起止页码：2329

外文期刊名：SCIENCE CHINA-LIFE SCIENCES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001004036100001)】；

基金：This work was supported by the National Science and Technology Major Projects (2021YFC2300704), the National Key Research and Development Program of China (2021YFA1301402, 2018YFA0903700), the Strategic Priority Research Program of Chinese Academy of Sciences (XDA24010400), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), and the National Natural Science Foundation of China (32270695, 31972881). We hope to acknowledge support from Lingang Laboratory (Shanghai, China). We thank Dr. Jianqing Xu (Shanghai Public Health Clinical Center) for providing us with VACV strain, Dr. Ziyu Li (Shanghai Pengzan Biotech Corp) for help with LNP production, Chao Shi (Laboratory of animal center, Institut Pasteur of Shanghai) for assistance with mouse immunization, and Miaolian Ma (Protein expression and purification platform, CAS Center for Excellence in Molecular Plant Sciences) for support with cell culture. We also thank Jie Gong, Jie Deng and Xintian Xu for their help with figure preparation and cell experiments.

语种：英文

外文关键词：monkeypox virus; enveloped and mature viron; multi-valent mRNA vaccines; immune response; neutralizing antibody

摘要：Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have been reported. Its causal agent, monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, Orthopoxviridae, that also includes vaccinia virus (VACV) and others. MPV produces two distinct forms of viral particles during its replication cycles: the enveloped viron (EV) that is released via exocytosis, and the mature viron (MV) that is discharged through lysis of host cells. This study was designed to develop multi-valent mRNA vaccines against monkeypox EV and MV surface proteins, and examine their efficacy and mechanism of action. Four mRNA vaccines were produced with different combinations of surface proteins from EV (A35R and B6R), MV (A29L, E8L, H3L and M1R), or EV and MV, and were administered in Balb/c mice to assess their immunogenicity potentials. A dynamic immune response was observed as soon as seven days after initial immunization, while a strong IgG response to all immunogens was detected with ELISA after two vaccinations. The higher number of immunogens contributed to a more robust total IgG response and correlating neutralizing activity against VACV, indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection. Further, the mRNA vaccines elicited an antigen-specific CD4(+) T cell response that is biased towards Th1. The mRNA vaccines with different combinations of EV and MV surface antigens protected a mouse model from a lethal dose VACV challenge, with the EV and MV antigens-combined vaccine offering the strongest protection. These findings provide insight into the protective mechanism of multi-valent mRNA vaccines against MPV, and also the foundation for further development of effective and safe mRNA vaccines for enhanced protection against monkeypox virus outbreak.