A potent Gc neutralizing antibody reveals architecture-dependent bispecific protection against SFTSV

作者：Hongjie Lu, Liushuai Li, Nan Zhang, Yajie Liu, Bingyan Liu, Yuzhu Sun, Jiayi Zhang, Shuning Liu, Jiajia Luo, Jun Min Liao, Kexin Lv, Xinyu Yue, Min Xu, Jiajia Zhao, Xiaoli Wu, Xinlei Chen, Chunhui Tao, Yuhong Guo, Zheng Zhang, Manli Wang, Yaoqing Chen · 发表于：Emerging Microbes & Infections · 年份：2026 · DOI：10.1080/22221751.2026.2645854 · 被引用次数：1 · 研究领域：Viral Infections and Immunology Research、Monoclonal and Polyclonal Antibodies Research、interferon and immune responses

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a mortality rate of up to 30%. Currently, there are no approved vaccines or therapeutics for clinical use. Although neutralizing antibodies against the viral glycoprotein Gn have been reported, their efficacy can be limited by epitope inaccessibility and viral escape. Here, we isolated human monoclonal antibodies from convalescent donors and identified multiple neutralizing antibodies targeting the Gc glycoprotein, including CAV-Gc-2H1, which binds a previously undefined epitope in Gc domain II and exhibits strong neutralizing activity. To enhance breadth and potency, we engineered bispecific antibodies (bsAbs) that co-engage Gn and Gc. Across several architectural formats, scFv-Ig bsAbs exhibited synergistic neutralization in vitro and complete protection in vivo, outperforming parental monospecific antibodies. Mechanistic studies revealed that these bsAbs block both viral attachment and membrane fusion. Our findings establish bsAbs as a promising therapeutic platform against SFTSV and provide a design framework for next-generation antivirals targeting bunyaviruses.