南方科技大学张政团队的最新研究提出了结构保守的人源抗A35抗体保护小鼠和猕猴免受猴痘病毒感染。该项研究成果发表在2025年8月26日出版的《细胞》上。

在这项研究中，课题组研究人员证明了两种人抗a35单克隆抗体（mAbs）在CAST/EiJ小鼠和恒河猴中显示出对MPXV的潜在保护作用。利用低温电子显微镜，小组确定了A35二聚体与mAb 975或mAb 981抗原结合片段复合物的两个高分辨率结构，揭示了抗原-抗体界面的详细相互作用。结构分析表明，这些结构保守的单抗结合到A35二聚体界面的凹槽区。总的来说，课题组研究人员提供了单次给药抗A35单抗减轻恒河猴MPXV感染的致病作用的概念证明。这些人类来源的单克隆抗体可以作为候选抗体，它们与A35二聚体的结合模型将为未来的疫苗设计提供有价值的见解。

据介绍，A35蛋白在猴痘病毒（MPXV）的包膜病毒粒子上表达，是病毒在宿主内感染和传播所必需的，使其成为有效的抗病毒靶点。

附：英文原文

Title: Structurally conserved human anti-A35 antibodies protect mice and macaques from mpox virus infection

Author: Bin Ju, Congcong Liu, Jingjing Zhang, Yaning Li, Haonan Yang, Bing Zhou, Baoying Huang, Jianrong Ma, Jiahan Lu, Lin Cheng, Zhe Cong, Lin Zhu, Tianhao Shi, Yuehong Sun, Na Li, Ting Chen, Miao Wang, Shilong Tang, Xiangyang Ge, Juanjuan Zhao, Wen-Jie Tan, Renhong Yan, Jing Xue, Zheng Zhang

Issue&Volume: 2025-08-26

Abstract: The A35 protein, expressed on the enveloped virion of monkeypox (mpox) virus (MPXV), is essential for viral infection and spread within the host, making it an effective antiviral target. In this study, we demonstrated two human anti-A35 monoclonal antibodies (mAbs) displayed potential protection against MPXV in CAST/EiJ mice and rhesus macaques. Using cryo-electron microscopy, we determined two high-resolution structures of the A35 dimer in complex with the fragment of antigen binding of mAb 975 or mAb 981, revealing detailed interactions at the antigen-antibody interfaces. Structural analysis showed that these structurally conserved mAbs bind to a groove region at the interface of A35 dimer. Overall, we provided a proof of concept for a single administration of anti-A35 mAbs mitigating the pathogenic effects of MPXV infection in rhesus macaques. These human-derived mAbs could be served as antibody drug candidates, and their binding models to the A35 dimer will provide valuable insights for future vaccine design.

DOI: 10.1016/j.cell.2025.08.005

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00919-5