Discovery and characterization of potent broadly neutralizing antibodies from human survivors of severe fever with thrombocytopenia syndrome

作者：Shuo Zhang, Hang Shang, Shuo Han, Jiachen Li, Xue‐Fang Peng, Yong‐Xiang Wu, Xin Yang, Yu Leng, Fengze Wang, Ning Cui, Lingjie Xu, Hongkai Zhang, Yu Guo, Xiaoyu Xu, Nan Zhang, Wei Liu, Hao Li · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2024.105481 · 被引用次数：21 · 研究领域：Viral Infections and Vectors、Viral Infections and Outbreaks Research、Vector-borne infectious diseases

BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus that causes viral hemorrhagic fever. Pandemic concerns have arisen due to the increased human-to-human transmission and high mortality rate, highlighting the urgent need for specific therapeutics. METHODS: Our observational study characterized the memory B cell response to natural SFTSV infection in four survivors. Monoclonal antibodies (mAbs) targeting the SFTSV glycoprotein N (Gn) were isolated and tested for in vitro neutralizing activities and effects on virus binding. Structural analysis was performed to identify neutralizing epitopes recognized by the mAbs. Prophylactical and therapeutical protections were evaluated using a lethal SFTSV infection model. FINDINGS: The selected mAbs exhibiting neutralizing activity primarily originate from the IGHV5-51 and IGHV3-30 germlines and target four distinct antigenic sites on SFTSV Gn. These elite mAbs effectively blocked the interaction between Gn and the cell receptor, preventing infections from five phylogenetically distinct SFTSV clades. Structural analysis revealed a novel neutralizing epitope located within SFTSV Gn domain I recognized by the elite mAbs. In mice of lethal infections with different SFTSV strains, administering a low dose of elite mAbs significantly improved survival rates in both prophylactic and therapeutic settings. INTERPRETATION: This study identifies potent broadly neutralizing antibodies that hol...