Generation and characterization of neutralizing antibodies against M1R and B6R proteins of monkeypox virus

Yuanyuan Qu, Wanbo Tai, Enhao Ma, Qiwei Jiang, Miao Fan, Wangcheng Xiao, Chongyu Tian, Yang Liu, Jianying Liu, Xinquan Wang, Jiwan Ge () and Gong Cheng ()
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Yuanyuan Qu: Shenzhen Bay Laboratory
Wanbo Tai: Shenzhen Bay Laboratory
Enhao Ma: Tsinghua University
Qiwei Jiang: Key Laboratory of Jilin Province for Zoonosis Prevention and Control
Miao Fan: Chinese Academy of Medical Sciences & Peking Union Medical College
Wangcheng Xiao: Shenzhen Bay Laboratory
Chongyu Tian: Shenzhen Bay Laboratory
Yang Liu: Shenzhen Bay Laboratory
Jianying Liu: Shenzhen Bay Laboratory
Xinquan Wang: Tsinghua University
Jiwan Ge: Chinese Academy of Medical Sciences & Peking Union Medical College
Gong Cheng: Tsinghua University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58180-z

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