Antibody-dependent-cellular-cytotoxicity-inducing antibodies significantly affect the post-exposure treatment of Ebola virus infection
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 μg/ml; ADCC EC50, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Scientific reports - 7(2017) vom: 30. März, Seite 45552 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Qiang [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 11.12.2018 Date Revised 11.12.2018 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/srep45552 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM27046462X |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC50, 0.018 μg/ml; ADCC EC50, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV | ||
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| 700 | 1 | |a Fan, Changfa |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Shuya |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Weijin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chunyun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Baowen |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Liangzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Youchun |e verfasserin |4 aut | |
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