文献类型： 外文期刊

作者： Quan, Chuansong ¹ ; Nie, Kaixiao ¹ ; Ma, Dezhen ⁴ ; Su, Chao ⁵ ; Li, Lianfeng ⁶ ; Zheng, Wenjun ¹ ; Yin, Chunhong ⁷ ; Wang, Yiwen ¹ ; Yang, Peipei ⁸ ; Peng, Dingkun ⁶ ; Liu, Xin ⁹ ; Li, Weiwei ¹⁰ ; Liu, Weixiao ¹¹ ; Shan, Chao ⁸ ; Zheng, Jie ⁹ ; Liu, Di ¹² ; Zhang, Hong ² ; Carr, Michael J. ¹³ ; Gao, George F. ¹⁰ ; Qi, Jianxun ¹⁰ ; Shi, Weifeng ⁹ ;

作者机构： 1.Shandong First Med Univ & Shandong Acad Med Sci, Key Lab Emerging Infect Dis Univ Shandong, Jinan, Peoples R China

2.Shandong First Med Univ, Affiliated Hosp 2, Dept Hematol, Tai An, Peoples R China

3.Shandong First Med Univ & Shandong Acad Med Sci, Sch Publ Hlth, Jinan, Peoples R China

4.Taian Ctr Dis Control & Prevent, Dept Vector Control, Tai An, Peoples R China

5.Southeast Univ, Adv Inst Life & Hlth, Sch Med, Jiangsu Prov Key Lab Crit Care Med, Nanjing, Peoples R China

6.Chinese Acad Agr Sci, State Key Lab Anim Dis Control & Prevent, Harbin Vet Res Inst, Harbin, Peoples R China

7.Shandong Ctr Dis Control & Prevent, Infect Dis Control Inst, Shandong Prov Key Lab Infect Dis Prevent & Control, Jinan, Peoples R China

8.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol & Biosafety, Wuhan, Peoples R China

9.Shanghai Jiao Tong Univ, Shanghai Inst Virol, Sch Med, Shanghai, Peoples R China

10.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

11.Taian Ctr Dis Control & Prevent, Dept Infect Dis Control & Prevent, Tai An, Peoples R China

12.Chinese Acad Sci, Ctr Biosafety Mega Sci, Wuhan Inst Virol, Key Lab Special Pathogens & Biosafety, Wuhan, Peoples R China

13.Univ Coll Dublin, Sch Med, Natl Virus Reference Lab, Dublin, Ireland

14.Hokkaido Univ, Int Inst Zoonosis Control, Int Collaborat Unit, Sapporo, Japan

15.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai, Peoples R China

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

页码：

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.