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A single-domain antibody inhibits SFTSV and mitigates virus-induced pathogenesis in vivo
Xilin Wu, Yanlei Li, Bilian Huang, Xiaohua Ma, Linjing Zhu, Nan Zheng, Shijie Xu, Waqas Nawaz, Changping Xu, Zhiwei Wu
Xilin Wu, Yanlei Li, Bilian Huang, Xiaohua Ma, Linjing Zhu, Nan Zheng, Shijie Xu, Waqas Nawaz, Changping Xu, Zhiwei Wu
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Research Article Infectious disease Therapeutics

A single-domain antibody inhibits SFTSV and mitigates virus-induced pathogenesis in vivo

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Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that recently emerged in East Asian countries. SFTS is characterized by high fever, thrombocytopenia, leukopenia, multiorgan failure, and hemorrhage with case fatality rates of 6.3% to 30%. Neither antivirals nor vaccines are available at present. We previously demonstrated that neutralizing antibodies specific for SFTSV glycoprotein (Gn) played a vital role in the survival of patients with SFTS. Nanobodies from camels present unique properties, such as thermostability, high affinity, and low immunogenicity. In the current study, mammalian expressed SFTSV Gn was used to immunize a camel, and functional nanobodies were isolated from the B cell nanobody library constructed from the immunized animal. Clone SNB02 was selected for in-depth analysis for its inhibition of SFTSV replication both in vitro and in vivo. We showed that SNB02 potently inhibited SFTSV infection and prevented thrombocytopenia in a humanized mouse model and is a potential candidate for therapeutics.

Authors

Xilin Wu, Yanlei Li, Bilian Huang, Xiaohua Ma, Linjing Zhu, Nan Zheng, Shijie Xu, Waqas Nawaz, Changping Xu, Zhiwei Wu

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Figure 3

Design and characterization of SNB02.

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Design and characterization of SNB02.
(A) Schematic diagram shows the st...
(A) Schematic diagram shows the structures of SNB, VHH + human Fc1 (CH2–3). (B) The graph shows the IC50 of 23 various SNBs, which were tested for neutralization against live SFTSV infection. The dashed line indicates that IC50 was more than 24 μg/mL. Twenty-three various SNBs binding with sGn protein identified by ELISA (C) and by SPR (D). All experiments were repeated twice.

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