抗M1R/B6R抗体的表征及用于增强正痘病毒防护的双特异性设计

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

作者信息

Zhao Runchu, Wu Lili, Zhang Yi, Ma Jianrong, Liu Dezhi, Zheng Yuxuan, Kong Tianxiang, Ma Renyi, Gao Zhengrong, Chai Yan, Liu Yuanlang, Tian Yi, Xia Yunxiang, Hou Yongzhi, Lu Jiahan, Cong Zhe, Huang Baoying, Tan Wenjie, Xue Jing, Gao George F, Wang Qihui

机构信息

Institute of Physical Science and Information, Anhui University, 230039, Hefei, Anhui, China.

CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), 100101, Beijing, China.

出版信息

EMBO Mol Med. 2025 Sep 8. doi: 10.1038/s44321-025-00299-z.

DOI:10.1038/s44321-025-00299-z

PMID:40921877

Abstract

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.

摘要

由猴痘病毒（MPXV）引起的人类猴痘全球爆发，凸显了对安全有效治疗方法的迫切需求。在本研究中，我们通过对免疫小鼠的单克隆抗体（MAb）进行测序，并通过体外和体内结合及抗病毒活性评估来分析其表位和功能，从而对主要的MPXV免疫原M1R和B6R进行了表征。鉴定出了几种具有广泛效力的抗M1R和抗B6R中和单克隆抗体，当用于抗体鸡尾酒和双特异性抗体设计时，它们对MPXV或痘苗病毒（VACV）表现出增强的抗病毒作用。值得注意的是，双特异性抗体的VH-CH1开关区域插入形式在小鼠模型中对VACV表现出强大的保护效力。总体而言，我们的研究对抗M1R和抗B6R单克隆抗体的表位和功能图谱进行了表征，并开发出了有前景的广谱抗体候选物，用于治疗MPXV和其他正痘病毒感染。