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

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

doi:10.3390/v14081665

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

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

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	1665
Journal	Viruses
Volume	14
Issue number	8
DOIs	https://doi.org/10.3390/v14081665
State	Published - Aug 2022

Keywords

SFTS virus
animal model
neutralization
severe fever with thrombocytopenia syndrome (SFTS)
therapeutic monoclonal antibody

ASJC Scopus subject areas

Infectious Diseases
Virology

Access to Document

10.3390/v14081665

Cite this

@article{4e781ea866ef401ea7022d1c61d3a512,

title = "Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model",

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.",

keywords = "SFTS virus, animal model, neutralization, severe fever with thrombocytopenia syndrome (SFTS), therapeutic monoclonal antibody",

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

note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = aug,

doi = "10.3390/v14081665",

language = "English (US)",

volume = "14",

journal = "Viruses",

issn = "1999-4915",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "8",

}

TY - JOUR

T1 - Neutralizing mAbs against SFTS Virus Gn Protein Show Strong Therapeutic Effects in an SFTS Animal Model

AU - Shimojima, Masayuki

AU - Sugimoto, Satoko

AU - Umekita, Kunihiko

AU - Onodera, Taishi

AU - Sano, Kaori

AU - Tani, Hideki

AU - Takamatsu, Yuki

AU - Yoshikawa, Tomoki

AU - Kurosu, Takeshi

AU - Suzuki, Tadaki

AU - Takahashi, Yoshimasa

AU - Ebihara, Hideki

AU - Saijo, Masayuki

PY - 2022/8

Y1 - 2022/8

N2 - 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.

AB - 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.

KW - SFTS virus

KW - animal model

KW - neutralization

KW - severe fever with thrombocytopenia syndrome (SFTS)

KW - therapeutic monoclonal antibody

UR - http://www.scopus.com/inward/record.url?scp=85136646636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85136646636&partnerID=8YFLogxK

U2 - 10.3390/v14081665

DO - 10.3390/v14081665

M3 - Article

C2 - 36016286

AN - SCOPUS:85136646636

SN - 1999-4915

VL - 14

JO - Viruses

JF - Viruses

IS - 8

M1 - 1665

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this