Development of an antibody cocktail for treatment of Sudan virus infection
Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:117 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 117(2020), 7 vom: 18. Feb., Seite 3768-3778 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Herbert, Andrew S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.07.2020 Date Revised 04.08.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1914985117 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306106426 |
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| 100 | 1 | |a Herbert, Andrew S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Development of an antibody cocktail for treatment of Sudan virus infection |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 10.07.2020 | ||
| 500 | |a Date Revised 04.08.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Sudan virus | |
| 650 | 4 | |a cocktail | |
| 650 | 4 | |a ebolavirus | |
| 650 | 4 | |a monoclonal antibody | |
| 650 | 4 | |a therapy | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Viral Proteins |2 NLM | |
| 700 | 1 | |a Froude, Jeffery W |e verfasserin |4 aut | |
| 700 | 1 | |a Ortiz, Ramon A |e verfasserin |4 aut | |
| 700 | 1 | |a Kuehne, Ana I |e verfasserin |4 aut | |
| 700 | 1 | |a Dorosky, Danielle E |e verfasserin |4 aut | |
| 700 | 1 | |a Bakken, Russell R |e verfasserin |4 aut | |
| 700 | 1 | |a Zak, Samantha E |e verfasserin |4 aut | |
| 700 | 1 | |a Josleyn, Nicole M |e verfasserin |4 aut | |
| 700 | 1 | |a Musiychuk, Konstantin |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, R Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Streatfield, Stephen J |e verfasserin |4 aut | |
| 700 | 1 | |a Wec, Anna Z |e verfasserin |4 aut | |
| 700 | 1 | |a Bohorova, Natasha |e verfasserin |4 aut | |
| 700 | 1 | |a Bohorov, Ognian |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Do H |e verfasserin |4 aut | |
| 700 | 1 | |a Pauly, Michael H |e verfasserin |4 aut | |
| 700 | 1 | |a Velasco, Jesus |e verfasserin |4 aut | |
| 700 | 1 | |a Whaley, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Stonier, Spencer W |e verfasserin |4 aut | |
| 700 | 1 | |a Bornholdt, Zachary A |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Zeitlin, Larry |e verfasserin |4 aut | |
| 700 | 1 | |a Sampey, Darryl |e verfasserin |4 aut | |
| 700 | 1 | |a Yusibov, Vidadi |e verfasserin |4 aut | |
| 700 | 1 | |a Dye, John M |e verfasserin |4 aut | |
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