Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model

针对 SFTS 病毒 Gn 蛋白的中和 mAb 在 SFTS 动物模型中表现出强大的治疗效果

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作者:Masayuki Shimojima, Satoko Sugimoto, Kunihiko Umekita, Taishi Onodera, Kaori Sano, Hideki Tani, Yuki Takamatsu, Tomoki Yoshikawa, Takeshi Kurosu, Tadaki Suzuki, Yoshimasa Takahashi, Hideki Ebihara, Masayuki Saijo

Abstract

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.

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