抗 SFTS 病毒 Gn 蛋白的中和单抗在 SFTS 动物模型中显示出强大的治疗效果。
Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model.
机构信息
Department of Virology I, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Department of Respirology, Rheumatology, Infectious Diseases and Neurology, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
出版信息
Viruses. 2022 Jul 28;14(8):1665. doi: 10.3390/v14081665.
Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease with a high case fatality rate caused by the SFTS virus, and currently there are no approved specific treatments. Neutralizing monoclonal antibodies (mAbs) against the virus could be a therapeutic agent in SFTS treatment, but their development has not sufficiently been carried out. In the present study, mouse and human mAbs exposed to the viral envelope proteins Gn and Gc (16 clones each) were characterized in vitro and in vivo by using recombinant proteins, cell culture with viruses, and an SFTS animal model with IFNAR mice. Neutralization activities against the recombinant vesicular stomatitis virus bearing SFTS virus Gn/Gc as envelope proteins were observed with three anti-Gn and six anti-Gc mAbs. Therapeutic activities were observed among anti-Gn, but not anti-Gc mAbs with neutralizing activities. These results propose an effective strategy to obtain promising therapeutic mAb candidates for SFTS treatment, and a necessity to reveal precise roles of the SFTS virus Gn/Gc proteins.
严重发热伴血小板减少综合征（SFTS）是一种传染病，由 SFTS 病毒引起，死亡率高，目前尚无批准的特效治疗方法。针对该病毒的中和单克隆抗体（mAbs）可能是 SFTS 治疗的一种治疗药物，但尚未充分开发。在本研究中，使用重组蛋白、带有病毒的细胞培养和 IFNAR 敲除小鼠的 SFTS 动物模型，对暴露于病毒包膜蛋白 Gn 和 Gc 的小鼠和人 mAbs（各 16 个克隆）进行了体外和体内特性分析。用三种抗 Gn 和六种抗 Gc mAbs 观察到对携带 SFTS 病毒 Gn/Gc 作为包膜蛋白的重组水疱性口炎病毒的中和活性。具有中和活性的抗 Gn mAb 具有治疗活性，而具有中和活性的抗 Gc mAb 则没有。这些结果为获得 SFTS 治疗有前途的治疗性 mAb 候选物提供了一种有效的策略，同时也需要揭示 SFTS 病毒 Gn/Gc 蛋白的确切作用。
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