A Potent Interdomain-Targeting Antibody Protects against SFTSV in Mice and Non-Human Primates
摘要
Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a growing global health threat with substantial mortality and no effective treatments. We report the discovery of ZS1C5, a human antibody that neutralizes SFTSV with subnanomolar potency by targeting a previously unknown interdomain epitope on glycoprotein Gn, mediated by an elongated CDRH3. A single dose of ZS1C5 conferred robust protection in both murine and, for the first time, non-human primate SFTSV infection models, demonstrating rapid viral control and immune restoration. Importantly, we applied a structure-guided mining approach to human B cell repertoires and identified germline-encoded ZS1C5-like antibodies, underscoring the potential for rapid recall of protective immunity. Together, these findings establish ZS1C5 as a promising clinical candidate and provide a blueprint for developing therapeutics and vaccines targeting interdomain epitopes in emerging bunyaviruses.
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- 2025-11-28 (2)
- 2025-11-28 (1)
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