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

Author:

Shimojima MasayukiORCID,Sugimoto Satoko,Umekita KunihikoORCID,Onodera TaishiORCID,Sano Kaori,Tani HidekiORCID,Takamatsu Yuki,Yoshikawa Tomoki,Kurosu Takeshi,Suzuki Tadaki,Takahashi Yoshimasa,Ebihara Hideki,Saijo Masayuki

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.

Funder

Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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