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

文献类型： 外文期刊

第一作者： Zhang, Niubing

作者： Zhang, Niubing;Cheng, Xiang;Li, Xuan;Zhu, Yilong;Li, Xiao;Mo, Ouyang;Yu, Huiqing;Zhu, Liqi;Zhang, Juan;Kuang, Linlin;Gao, Ying;Liang, Xiaozhen;Wang, Haikun;Hao, Pei;Cao, Ruiyuan;Li, Song;Zhong, Wu;Zhu, Yilong;Zhang, Niubing;Li, Honglin;Zhang, Niubing;Li, Honglin;Cheng, Xiang;Mo, Ouyang;Zhu, Liqi;Zhang, Juan;Gao, Ying;Liang, Xiaozhen;Wang, Haikun;Li, Xuan;Hao, Pei

作者机构：

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

期刊名称：SCIENCE CHINA-LIFE SCIENCES （ 影响因子：9.1； 五年影响因子：7.1 ）

ISSN： 1674-7305

年卷期： 2023 年

页码：

收录情况： SCI

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.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序