A broadly protective antibody targeting glycoprotein Gn inhibits severe fever with thrombocytopenia syndrome virus infection

Xuanxiu Ren, Jiawen Sun, Wenhua Kuang, Feiyang Yu, Bingjie Wang, Yong Wang, Wei Deng, Zhao Xu, Shangyu Yang, Hualin Wang, Yangbo Hu, Zengqin Deng (), Yun-Jia Ning () and Haiyan Zhao ()
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Xuanxiu Ren: Wuhan University
Jiawen Sun: Chinese Academy of Sciences
Wenhua Kuang: Chinese Academy of Sciences
Feiyang Yu: Wuhan University
Bingjie Wang: Wuhan University
Yong Wang: Chinese Academy of Sciences
Wei Deng: Chinese Academy of Sciences
Zhao Xu: Chinese Academy of Sciences
Shangyu Yang: Wuhan University
Hualin Wang: Chinese Academy of Sciences
Yangbo Hu: Chinese Academy of Sciences
Zengqin Deng: Chinese Academy of Sciences
Yun-Jia Ning: Chinese Academy of Sciences
Haiyan Zhao: Wuhan University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.

Date: 2024
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DOI: 10.1038/s41467-024-51108-z

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