数字农科院2.0

Molecular mechanism of potently neutralizing human monoclonal antibodies against severe fever with thrombocytopenia virus infection

文献类型： 外文期刊

作者： Quan, Chuansong;Nie, Kaixiao;Ma, Dezhen;Su, Chao;Li, Lianfeng;Zheng, Wenjun;Yin, Chunhong;Wang, Yiwen;Yang, Peipei;Peng, Dingkun;Liu, Xin;Li, Weiwei;Liu, Weixiao;Shan, Chao;Zheng, Jie;Liu, Di;Zhang, Hong;Carr, Michael J.;Gao, George F.;Qi, Jianxun;Shi, Weifeng

作者机构：

关键词： severe fever with thrombocytopenia syndrome;SFTSV;Bandavirus dabieense;monoclonal antibodies;neutralization;therapeutics

期刊名称： JOURNAL OF VIROLOGY

ISSN： 0022-538X

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Although severe fever with thrombocytopenia syndrome (SFTS) was first described in China in 2009, the case fatality rate remains >40% among patients with multi-organ failure. To date, no antivirals specifically targeting SFTSV have been approved. We obtained several monoclonal antibodies (mAbs) from SFTS survivors by single-cell RNA-seq. Neutralization and animal experiments were applied to assess the effects of these mAbs in vitro and in vivo, and co-crystal structures with SFTSV-Gn glycoproteins were determined by X-ray crystallography. The mAbs SD4, SD12, and SD22 targeted the SFTSV-Gn with high neutralizing activities, and, remarkably, SD4 and SD22 exhibited K-D values in the range of 32-83 pM for different viral genotypes. Notably, a single administration (20 mg/kg) of SD4 and SD22 showed 100% protection in mice at day 3 post-inoculation (dpi). Importantly, SD4 also provided 60% protection at a lower dose (0.3 mg/kg) when administered at 3 dpi. The crystallographic structures of SD4, SD22, and SD12 with Gn were determined at 3.3 & Aring;, 2.8 & Aring;, and 2.4 & Aring;, respectively, which revealed that they recognized a conserved antigenic epitope around the hexon wellhead edge. These human-derived mAbs have significant therapeutic potential for severe SFTS cases and provide a basis for rational antibody-based vaccine designs and clinical trials.

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