Tai Wanbo, Tian Chongyu, Shi Huicheng, Chai Benjie, Yu Xinyang, Zhuang Xinyu, Dong Pengyuan, Li Min, Yin Qi, Feng Shengyong, Wang Weixiao, Zhang Oujia, Liang Shibo, Liu Yang, Liu Jianying, Zhu Longchao, Zhao Guangyu, Tian Mingyao, Yu Guocan, Cheng Gong
Institute of Infectious Diseases, Shenzhen Bay Laboratory, Shenzhen, China.
New Cornerstone Science Laboratory, Tsinghua-Peking Joint Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
Nat Commun. 2025 Mar 26;16(1):2971. doi: 10.1038/s41467-025-58328-x.
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.
持续的猴痘疫情加剧了对猴痘疫苗的需求。基于信使核糖核酸（mRNA）疫苗平台，我们对来自细胞外被膜病毒（EVs）和细胞内成熟病毒（MVs）这两种病毒颗粒的猴痘病毒（MPXV）表面蛋白进行了系统筛选。此次筛选揭示了12种具有不同水平中和免疫原性的重要抗原。进一步评估表明，这些抗原中的4种、8种和12种抗原的组合，即Mix-4、Mix-8和Mix-12，可诱导不同程度的免疫保护，其中Mix-12的效果最为显著。这一发现不仅证明了中和抗体水平的重要性，还证明了其多样性在提供有效免疫保护方面的重要性。此外，我们采用了T细胞表位富集策略，分析MPXV的完整蛋白质组序列以预测富含抗原表位的区域。将这些富含表位的区域整合到一种名为MPX-EPs的细胞免疫靶向抗原中，表明一种细胞免疫靶向mRNA疫苗可独立提供免疫保护。此外，Mix-12与MPX-EPs联合免疫可实现对MPXV攻击的完全保护。总体而言，这些结果提示了一种通过体液免疫和细胞免疫反应的特异性协同来增强mRNA疫苗免疫保护的有效方法。
