中国科学院微生物研究所高福等研究人员合作发现，合理设计的“二合一”免疫原DAM驱动对猴痘病毒的强效免疫反应。相关论文于2024年1月5日在线发表于国际学术期刊《自然—免疫学》。

研究人员利用结构引导的多抗原融合策略设计了一种“二合一”免疫原，它基于单链二聚体猴痘病毒（MPXV）胞外包膜病毒抗原A35与胞内成熟病毒抗原M1的双价融合，称为DAM。DAM保留了这两种成分的天然表位构型，与联合免疫策略相比，显示出更强的A35特异性抗体和M1特异性抗体反应，以及对疫苗病毒（VACV）的体内保护效力。

DAM诱导的MPXV特异性中和抗体是VACV活疫苗诱导抗体的28倍。铝佐剂DAM疫苗能保护小鼠免受致命的VACV挑战，且安全性良好，中试规模生产证实了DAM的高产量和高纯度。因此，这项研究为开发针对MPXV和其他正痘病毒的替代疫苗提供了创新见解和候选免疫原。

研究人员表示，2022年MPXV在全球爆发，凸显了对更安全、更易获得的新一代疫苗的迫切需求。

附：英文原文

Title: Rational design of a ‘two-in-one’ immunogen DAM drives potent immune response against monkeypox virus

Author: Wang, Han, Yin, Peng, Zheng, Tingting, Qin, Lanju, Li, Shihua, Han, Pu, Qu, Xiao, Wen, Jun, Ding, Haoyi, Wu, Jiahao, Kong, Tianxiang, Gao, Zhengrong, Hu, Songtao, Zhao, Xin, Cao, Xiangyu, Fang, Min, Qi, Jianxun, Xi, Jianzhong Jeff, Duan, Kai, Yang, Xiaoming, Zhang, Zhuobing, Wang, Qihui, Tan, Wenjie, Gao, George Fu

Issue&Volume: 2024-01-05

Abstract: The global outbreak of the monkeypox virus (MPXV) in 2022 highlights the urgent need for safer and more accessible new-generation vaccines. Here, we used a structure-guided multi-antigen fusion strategy to design a ‘two-in-one’ immunogen based on the single-chain dimeric MPXV extracellular enveloped virus antigen A35 bivalently fused with the intracellular mature virus antigen M1, called DAM. DAM preserved the natural epitope configuration of both components and showed stronger A35-specific and M1-specific antibody responses and in vivo protective efficacy against vaccinia virus (VACV) compared to co-immunization strategies. The MPXV-specific neutralizing antibodies elicited by DAM were 28 times higher than those induced by live VACV vaccine. Aluminum-adjuvanted DAM vaccines protected mice from a lethal VACV challenge with a safety profile, and pilot-scale production confirmed the high yield and purity of DAM. Thus, our study provides innovative insights and an immunogen candidate for the development of alternative vaccines against MPXV and other orthopoxviruses.

DOI: 10.1038/s41590-023-01715-7

Source: https://www.nature.com/articles/s41590-023-01715-7