» Articles » PMID: 39888973

Pair Combinations of Human Monoclonal Antibodies Fully Protected Mice Against Bunyavirus SFTSV Lethal Challenge

Overview
Journal PLoS Pathog
Date 2025 Jan 31
PMID 39888973
Authors
Affiliations
Soon will be listed here.
Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever caused by a tick-borne virus SFTSV with a mortality rate of up to 30%. Currently, there is no vaccine or effective therapy for SFTS. Neutralizing monoclonal antibody therapy, which provides immediate passive immunity and may limit disease progression, has emerged as a reliable approach for developing therapeutic drugs for SFTS. In this study, 4 human monoclonal antibodies (hmAbs) derived from convalescent SFTS patients' lymphocytes based on human single-chain variable fragment antibody libraries were tested for their neutralizing activities in cells and their treatment effect in animals individually and in pair combinations. The neutralization test showed that all 4 hmAbs exhibited strong neutralizing activity against SFTSV infection in vitro. The protection rate of hmAbs 4-6, 1F6, 1B2, and 4-5 against SFTSV lethal challenge in IFNAR1-/- A129 mice are 50%, 16.7%, 83.3%, and 66.7%, respectively. Notably, the pair combination of antibodies (1B2 and 4-5, 1B2 and 1F6) that recognized distinct epitopes protected 100% of mice against SFTSV lethal challenge. In conclusion, our findings indicate that the pair combinations of hmAbs 1B2 and 4-5 or hmAbs 1B2 and 1F6 may serve as promising therapeutic drugs for treating SFTSV infection.

References
1.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

2.
Wang C, Li W, Drabek D, Okba N, van Haperen R, Osterhaus A . A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun. 2020; 11(1):2251. PMC: 7198537. DOI: 10.1038/s41467-020-16256-y. View

3.
Li A, Katinger H, Posner M, Cavacini L, Zolla-Pazner S, Gorny M . Synergistic neutralization of simian-human immunodeficiency virus SHIV-vpu+ by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins. J Virol. 1998; 72(4):3235-40. PMC: 109792. DOI: 10.1128/JVI.72.4.3235-3240.1998. View

4.
Liu Y, Wu B, Paessler S, Walker D, Tesh R, Yu X . The pathogenesis of severe fever with thrombocytopenia syndrome virus infection in alpha/beta interferon knockout mice: insights into the pathologic mechanisms of a new viral hemorrhagic fever. J Virol. 2013; 88(3):1781-6. PMC: 3911604. DOI: 10.1128/JVI.02277-13. View

5.
Kim K, Kim J, Ko M, Chun J, Kim H, Kim S . An anti-Gn glycoprotein antibody from a convalescent patient potently inhibits the infection of severe fever with thrombocytopenia syndrome virus. PLoS Pathog. 2019; 15(2):e1007375. PMC: 6380599. DOI: 10.1371/journal.ppat.1007375. View