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

Viruses. 2022 Jul 28;14(8):1665. doi: 10.3390/v14081665.

Authors

Affiliations

¹ Department of Virology I, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
² Department of Respirology, Rheumatology, Infectious Diseases and Neurology, Internal Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
³ Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
⁴ Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
⁵ Department of Virology, Toyama Institute of Health, Toyama 939-0363, Japan.
⁶ Department of Virology, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan.
⁷ Medical Affairs Department, Health and Welfare Bureau, Sapporo 060-0042, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / therapeutic use
Antibodies, Neutralizing / therapeutic use
Antibodies, Viral / therapeutic use
Disease Models, Animal
Humans
Mice
Phlebovirus*
Severe Fever with Thrombocytopenia Syndrome*
Viral Envelope Proteins / metabolism

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Viral Envelope Proteins

Supplementary concepts

SFTS phlebovirus

Grants and funding

This research was funded by JSPS KAKENHI Grant Numbers JP16K08041, JP18KK0232 and JP19K06414 and AMED Grant Numbers JP16fk0108102, JP17fk0108202, JP18fk01080002, JP19fk0108080, JP20fk0108080, JP21fk0108080, JP19fk0108081, JP20fk0108081 and JP21fk0108081.