Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV.
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Data availability
The monoclonal antibody sequences reported in this paper have been deposited in the NCBI database (B1D6 HC variable region, MW514299.1; B1D6 LC variable region, MW514300.1; C3A11 HC variable region, MW514301.1; C3A11 LC variable region, MW514302.1; C6C1 HC variable region, MW514305.1; C6C1 LC variable region, MW514306.1; C4H12 HC variable region, MW514303.1; and C4H12 LC variable region, MW514304.1).
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Acknowledgments
The Chinese SFTSV strain HB-29 was a gift from Dr. Dexin Li and Dr. Mifang Liang of the National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention.
Funding
This work was supported in part by the Emerging/Re-emerging Infectious Diseases Project of Japan from the Japan Agency for Medical Research and Development (AMED) under grant number JP23fk0108625 and the Interdisciplinary Cutting-Edge Research Program from AMED under grant number JP23wm0325034. The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Conceptualization, KS, TS; methodology, KS, MK, HT; investigation, KS, MK, AK, HT, HH, TS; data curation, KS, MK; formal analysis and visualization, KS; funding acquisition, HT, TS; project administration and supervision, HH, TS; writing – original draft, KS; writing – review and editing, KS, TS. All authors agreed to submit the manuscript, read and approved the final draft, and take full responsibility of its content including the accuracy of the data and statistical analysis.
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Communicated by Hideki Ebihara
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Sano, K., Kimura, M., Sataka, A. et al. Characterization of antibodies targeting severe fever with thrombocytopenia syndrome virus glycoprotein Gc. Arch Virol 169, 40 (2024). https://doi.org/10.1007/s00705-024-05968-x
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DOI: https://doi.org/10.1007/s00705-024-05968-x