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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 6

Evaluation of SNB02 therapeutic efficacy in SFTSV-infected NCG-HuPBL mice.

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Evaluation of SNB02 therapeutic efficacy in SFTSV-infected NCG-HuPBL mic...
WBCs (A), neutrophils (B), lymphocytes (C), and monocytes (D) were analyzed in 3 groups of NCG-HuPBL mice infected with SFTSV and treated with or without SNB02: SNB02 treatment 1 hour after SFTSV challenge (red, n = 8, 4 M + 4 F), SNB02 treatment 1 day after SFTSV challenge (green, n = 8, 4 M + 4 F). NCG-HuPBL mice infected with SFTSV but treated with PBS served as controls (black, n = 8, 4 M + 4 F). The normal range is between the 2 dashed lines. Each dot represents data from 1 mouse. (E) Body weight of mice among the above 3 groups. Each line represents data from 1 group. Data represent mean ± SEM; 1-way ANOVA with Bonferroni’s multiple comparison was used for statistical analysis. ns, no significance.

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