Anti-M1R/B6R antibody characterization and bispecific design for enhanced orthopoxvirus protection

作者：Runchu Zhao, Lili Wu, Yi Zhang, Jianrong Ma, Dezhi Liu, Yuxuan Zheng, Tianxiang Kong, Renyi Ma, Zhengrong Gao, Yan Chai, Yuanlang Liu, Yi Tian, Yunxiang Xia, Yongzhi Hou, Jiahan Lu, Zhe Cong, Baoying Huang, Wenjie Tan, Jing Xue, George F. Gao, Qihui Wang · 发表于：EMBO Molecular Medicine · 年份：2025 · DOI：10.1038/s44321-025-00299-z · 被引用次数：9 · 研究领域：Poxvirus research and outbreaks、Virus-based gene therapy research、Herpesvirus Infections and Treatments

The global outbreak of the mpox in humans, caused by the mpox virus (MPXV), underscores the urgent need for safe and effective therapeutics. In this study, we characterized the dominant MPXV immunogens, M1R and B6R, by sequencing monoclonal antibodies (MAbs) from the immunized mice and analyzing their epitopes and functions through in vitro and in vivo assessments of binding and antiviral activities. Several broadly effective anti-M1R and anti-B6R neutralizing MAbs were identified and they exhibited enhanced antiviral effects against MPXV or vaccinia virus (VACV) when used in antibody cocktail and bispecific antibody designs. Notably, the VH-CH1 switch region-inserting format of bispecific antibodies exhibited robust protective efficacy against VACV in a mouse model. Collectively, our study characterized the epitope and functional maps of anti-M1R and anti-B6R MAbs and developed promising broad-spectrum antibody candidates for the treatment of MPXV and other orthopoxvirus infections.