Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge.
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...
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| Format: | Article |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012889 |
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| author | Bang Li Xiang-Rong Qin Jia-Chen Qu Guan-du Wu Wen-Kang Zhang Ze-Zheng Jiang Pan-Pan Liu Ze-Min Li Tian-Mei Yu Chuan-Min Zhou Yong-Jun Jiao Xue-Jie Yu |
| author_facet | Bang Li Xiang-Rong Qin Jia-Chen Qu Guan-du Wu Wen-Kang Zhang Ze-Zheng Jiang Pan-Pan Liu Ze-Min Li Tian-Mei Yu Chuan-Min Zhou Yong-Jun Jiao Xue-Jie Yu |
| author_sort | Bang Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fc72047f7e294fdcbb622d30527af03a |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-fc72047f7e294fdcbb622d30527af03a2025-02-07T05:30:30ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101288910.1371/journal.ppat.1012889Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge.Bang LiXiang-Rong QinJia-Chen QuGuan-du WuWen-Kang ZhangZe-Zheng JiangPan-Pan LiuZe-Min LiTian-Mei YuChuan-Min ZhouYong-Jun JiaoXue-Jie YuSevere 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.https://doi.org/10.1371/journal.ppat.1012889 |
| spellingShingle | Bang Li Xiang-Rong Qin Jia-Chen Qu Guan-du Wu Wen-Kang Zhang Ze-Zheng Jiang Pan-Pan Liu Ze-Min Li Tian-Mei Yu Chuan-Min Zhou Yong-Jun Jiao Xue-Jie Yu Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. PLoS Pathogens |
| title | Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. |
| title_full | Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. |
| title_fullStr | Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. |
| title_full_unstemmed | Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. |
| title_short | Pair combinations of human monoclonal antibodies fully protected mice against bunyavirus SFTSV lethal challenge. |
| title_sort | pair combinations of human monoclonal antibodies fully protected mice against bunyavirus sftsv lethal challenge |
| url | https://doi.org/10.1371/journal.ppat.1012889 |
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