An mRNA vaccine against monkeypox virus inhibits infection by co-activation of humoral and cellular immune responses
Abstract
The persistent monkeypox outbreaks intensify the demand for monkeypox vaccines. Based on the mRNA vaccine platform, we conduct a systematic screening of monkeypox virus (MPXV) surface proteins from two types of viral particles, extracellular enveloped viruses (EVs) and intracellular mature viruses (MVs). This screening unveils 12 important antigens with diverse levels of neutralizing immunogenicity. Further assessment reveals that the combinations of 4, 8, and 12 of these antigens, namely Mix-4, Mix-8, and Mix-12, induce varying degrees of immune protection, with Mix-12 being the most potent. This finding demonstrates the significance of not only the level but also the diversity of the neutralizing antibodies in providing potent immune protection. Additionally, we utilize a T cell-epitope enrichment strategy, analyzing the complete proteome sequence of the MPXV to predict antigenic epitope-rich regions. Integration of these epitope-rich regions into a cellular immune-targeting antigen, named MPX-EPs, showcases that a cellular immune-targeting mRNA vaccine can independently confer immune protection. Furthermore, co-immunization with Mix-12 and MPX-EPs achieves complete protection against MPXV challenge. Overall, these results suggest an effective approach to enhance the immune protection of mRNA vaccines through the specific coordination of humoral and cellular immune responses.
Authors
Wanbo Tai, Chongyu Tian, Huicheng Shi, Benjie Chai, Xinyang Yu, Xinyu Zhuang, Pengyuan Dong, Min Li, Qi Yin, Shengyong Feng, Weixiao Wang, Oujia Zhang, Shibo Liang, Yang Liu, Jianying Liu, Longchao Zhu, Guangyu Zhao, Mingyao Tian, Guocan Yu & Gong Cheng
Journal Information
Nature Communications (2025)
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Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus
Abstract
The global outbreak of monkeypox virus (MPXV), combined with the termination of smallpox vaccination and the lack of specific antiviral treatments, raises increasing concerns. The surface proteins M1R and B6R of MPXV are crucial for virus transmission and serve as key targets for vaccine development. In this study, a panel of human antibodies targeting M1R and B6R is isolated from a human antibody library using phage display technology. Among these antibodies, A138 against M1R and B026 against B6R show the most potent broad-spectrum neutralizing activities against MPXV and Vaccinia virus (VACV). When used in combination, A138 and B026 exhibit complementary neutralizing activity against both viruses in vitro. X-ray crystallography reveales that A138 binds to the loop regions of M1R, similar to the vulnerable epitope of 7D11 on VACV L1R. By contrast, A129 targets a more cryptic epitope, primarily comprising the β-strands of M1R. Moreover, prophylactic and therapeutic administration of A138 or B026 alone provides partial protection, while combining these two antibodies results in enhanced protection against VACV in male C57BL/6 mice. This study demonstrates of a dual-targeting strategy using two different components of the virion for the prevention and treatment of MPXV infection.
Authors
Yuanyuan Qu, Wanbo Tai, Enhao Ma, Qiwei Jiang, Miao Fan, Wangcheng Xiao, Chongyu Tian, Yang Liu, Jianying Liu, Xinquan Wang, Jiwan Ge & Gong Cheng
Journal Information
Nature Communications (2025)
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