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

文献类型： 外文期刊

第一作者： Quan, Chuansong

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

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

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：3.8； 五年影响因子：3.9 ）

ISSN： 0022-538X

年卷期： 2025 年 99 卷 7 期

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收录情况： SCI

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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