Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge

• Published in: PLoS pathogens 2025-01, Vol.21 (1), p.e1012889
• Main Authors: Li, Bang, Qin, Xiang-Rong, Qu, Jia-Chen, Wu, Guan-du, Zhang, Wen-Kang, Jiang, Ze-Zheng, Liu, Pan-Pan, Li, Ze-Min, Yu, Tian-Mei, Zhou, Chuan-Min, Jiao, Yong-Jun, Yu, Xue-Jie
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Neutralizing - immunology; Antibodies, Neutralizing - therapeutic use; Antibodies, Viral - immunology; Bunyaviridae Infections - immunology; Bunyaviridae Infections - prevention & control; Female; Humans; Mice; Phlebovirus - immunology; Severe Fever with Thrombocytopenia Syndrome - immunology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1012889

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.