Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection
Copyright © 2018 Elsevier Inc. All rights reserved..
Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates.
| Errataetall: |
CommentIn: Cell Host Microbe. 2019 Jan 9;25(1):10-12. - PMID 30629912 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
Cell host & microbe - 25(2019), 1 vom: 09. Jan., Seite 39-48.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wec, Anna Z [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.03.2019 Date Revised 06.10.2023 published: Print CommentIn: Cell Host Microbe. 2019 Jan 9;25(1):10-12. - PMID 30629912 Citation Status MEDLINE |
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| doi: |
10.1016/j.chom.2018.12.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292581947 |
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| 245 | 1 | 0 | |a Development of a Human Antibody Cocktail that Deploys Multiple Functions to Confer Pan-Ebolavirus Protection |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 14.03.2019 | ||
| 500 | |a Date Revised 06.10.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a CommentIn: Cell Host Microbe. 2019 Jan 9;25(1):10-12. - PMID 30629912 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 Elsevier Inc. All rights reserved. | ||
| 520 | |a Passive administration of monoclonal antibodies (mAbs) is a promising therapeutic approach for Ebola virus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development are specific for a single member of the Ebolavirus genus, Ebola virus (EBOV), and ineffective against outbreak-causing Bundibugyo virus (BDBV) and Sudan virus (SUDV). Here, we advance MBP134, a cocktail of two broadly neutralizing human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity, as a candidate pan-ebolavirus therapeutic. MBP134 potently neutralized all ebolaviruses and demonstrated greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, engineered to effectively harness natural killer (NK) cells afforded additional improvement relative to its precursor in protective efficacy against EBOV and SUDV in guinea pigs. MBP134AF is an optimized mAb cocktail suitable for evaluation as a pan-ebolavirus therapeutic in nonhuman primates | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Ebola glycoprotein | |
| 650 | 4 | |a Ebola virus | |
| 650 | 4 | |a antibody cocktail | |
| 650 | 4 | |a antibody engineering | |
| 650 | 4 | |a antiviral drug | |
| 650 | 4 | |a broadly neutralizing antibodies | |
| 650 | 4 | |a ebolavirus | |
| 650 | 4 | |a filovirus | |
| 650 | 4 | |a human monoclonal antibodies | |
| 650 | 4 | |a immunotherapy | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
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| 700 | 1 | |a He, Shihua |e verfasserin |4 aut | |
| 700 | 1 | |a Herbert, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Goodwin, Eileen |e verfasserin |4 aut | |
| 700 | 1 | |a Wirchnianski, Ariel S |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhu, Wenjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Guodong |e verfasserin |4 aut | |
| 700 | 1 | |a Abelson, Dafna M |e verfasserin |4 aut | |
| 700 | 1 | |a Moyer, Crystal L |e verfasserin |4 aut | |
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| 700 | 1 | |a James, Rebekah M |e verfasserin |4 aut | |
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| 700 | 1 | |a Bohorova, Natasha |e verfasserin |4 aut | |
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| 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 Bortz, Robert H |c 3rd |e verfasserin |4 aut | |
| 700 | 1 | |a Whaley, Kevin J |e verfasserin |4 aut | |
| 700 | 1 | |a Goldstein, Tracey |e verfasserin |4 aut | |
| 700 | 1 | |a Anthony, Simon J |e verfasserin |4 aut | |
| 700 | 1 | |a Alter, Galit |e verfasserin |4 aut | |
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| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
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