Preprint / Version 2

A Potent Interdomain-Targeting Antibody Protects against SFTSV in Mice and Non-Human Primates

This article is a preprint and has not been certified by peer review.

Authors

Categories
Immunology & Microbiology
Keywords
SFTSV; Neutralizing antibody; Interdomain epitope; Non-human primates

Abstract

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.

Metrics

Favorites: 1
Views: 953
Downloads: 377

DOI:

https://doi.org/10.65215/apb7tn58

Submission ID:

34

Downloads

Additional Files

Supplemental File(s)

Posted

2025-11-28

Versions

How to Cite

Bi, J., Dai, Z., Hong, X., Zhang, Y., Lu, S., Wang, Q., Liu, Y., Li, X., Li, M., Song, G., Chen, Q., Yu, W., Yang, Y., Ma, Y., Liu, H., Meng, X., Wang, Z., Liu, D., Sun, R., … Li, D. (2025). A Potent Interdomain-Targeting Antibody Protects against SFTSV in Mice and Non-Human Primates. LangTaoSha Preprint Server. https://doi.org/10.65215/apb7tn58

Declaration of Competing Interests

The authors declare no competing interests to disclose.

Copyright

The copyright holder for this preprint is the author/funder.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.