Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model
Ebola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negativ...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2392651 |
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| author | Wujian Li Wanying Yang Xueqin Liu Wujie Zhou Shen Wang Zhenshan Wang Yongkun Zhao Na Feng Tiecheng Wang Meng Wu Liangpeng Ge Xianzhu Xia Feihu Yan |
| author_facet | Wujian Li Wanying Yang Xueqin Liu Wujie Zhou Shen Wang Zhenshan Wang Yongkun Zhao Na Feng Tiecheng Wang Meng Wu Liangpeng Ge Xianzhu Xia Feihu Yan |
| author_sort | Wujian Li |
| collection | DOAJ |
| description | Ebola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negative effect of decoy protein on the therapeutic efficacy of antibodies highlight the necessity of developing novel antibodies to counter the threat of Ebola. Here, 11 fully human mAbs were isolated from transgenic mice immunized with GP protein and recombinant vesicular stomatitis virus-bearing GP (rVSV-EBOV GP). These mAbs were divided into five groups according to their germline genes and exhibited differential binding activities and neutralization capabilities. In particular, mAbs 8G6, 2A4, and 5H4 were cross-reactive and bound at least three ebolavirus glycoproteins. mAb 4C1 not only exhibited neutralizing activity but no cross-reaction with sGP. mAb 7D8 exhibited the strongest neutralizing capacity. Further analysis on the critical residues for the bindings of 4C1 and 8G6 to GPs was conducted using antibodies complementarity-determining regions (CDRs) alanine scanning. It has been shown that light chain CDR3 played a crucial role in binding and neutralization and that any mutation in CDRs could not improve the binding of 4C1 to sGP. Importantly, mAbs 7D8, 8G6, and 4C1 provided complete protections against EBOV infection in a hamster lethal challenge model when administered 12 h post-infection. These results support mAbs 7D8, 8G6, and 4C1 as potent antibody candidates for further investigations and pave the way for further developments of therapies and vaccines. |
| format | Article |
| id | doaj-art-8eda2434f93341e8b1ad66aa4b641510 |
| institution | Kabale University |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-8eda2434f93341e8b1ad66aa4b6415102024-12-07T04:40:17ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2392651Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster modelWujian Li0Wanying Yang1Xueqin Liu2Wujie Zhou3Shen Wang4Zhenshan Wang5Yongkun Zhao6Na Feng7Tiecheng Wang8Meng Wu9Liangpeng Ge10Xianzhu Xia11Feihu Yan12College of Veterinary Medicine, Jilin University, Changchun, People’s Republic of ChinaDepartment of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, People’s Republic of ChinaChongqing Academy of Animal Sciences, Chongqing, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaChongqing Academy of Animal Sciences, Chongqing, People’s Republic of ChinaChongqing Academy of Animal Sciences, Chongqing, People’s Republic of ChinaCollege of Veterinary Medicine, Jilin University, Changchun, People’s Republic of ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, People’s Republic of ChinaEbola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negative effect of decoy protein on the therapeutic efficacy of antibodies highlight the necessity of developing novel antibodies to counter the threat of Ebola. Here, 11 fully human mAbs were isolated from transgenic mice immunized with GP protein and recombinant vesicular stomatitis virus-bearing GP (rVSV-EBOV GP). These mAbs were divided into five groups according to their germline genes and exhibited differential binding activities and neutralization capabilities. In particular, mAbs 8G6, 2A4, and 5H4 were cross-reactive and bound at least three ebolavirus glycoproteins. mAb 4C1 not only exhibited neutralizing activity but no cross-reaction with sGP. mAb 7D8 exhibited the strongest neutralizing capacity. Further analysis on the critical residues for the bindings of 4C1 and 8G6 to GPs was conducted using antibodies complementarity-determining regions (CDRs) alanine scanning. It has been shown that light chain CDR3 played a crucial role in binding and neutralization and that any mutation in CDRs could not improve the binding of 4C1 to sGP. Importantly, mAbs 7D8, 8G6, and 4C1 provided complete protections against EBOV infection in a hamster lethal challenge model when administered 12 h post-infection. These results support mAbs 7D8, 8G6, and 4C1 as potent antibody candidates for further investigations and pave the way for further developments of therapies and vaccines.https://www.tandfonline.com/doi/10.1080/22221751.2024.2392651Ebola virus diseaseEbola virusneutralizing antibodiesfully human antibodytransgenic micesurrogate model |
| spellingShingle | Wujian Li Wanying Yang Xueqin Liu Wujie Zhou Shen Wang Zhenshan Wang Yongkun Zhao Na Feng Tiecheng Wang Meng Wu Liangpeng Ge Xianzhu Xia Feihu Yan Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model Emerging Microbes and Infections Ebola virus disease Ebola virus neutralizing antibodies fully human antibody transgenic mice surrogate model |
| title | Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model |
| title_full | Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model |
| title_fullStr | Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model |
| title_full_unstemmed | Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model |
| title_short | Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model |
| title_sort | fully human monoclonal antibodies against ebola virus possess complete protection in a hamster model |
| topic | Ebola virus disease Ebola virus neutralizing antibodies fully human antibody transgenic mice surrogate model |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2392651 |
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