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Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic
Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228268/ https://www.ncbi.nlm.nih.gov/pubmed/35745509 http://dx.doi.org/10.3390/pathogens11060655 |
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author | Kuang, Erin Cross, Robert W. McCavitt-Malvido, Maria Abelson, Dafna M. Borisevich, Viktoriya Stuart, Lauren Agans, Krystle N. Mlakar, Neil Marimuthu, Arumugapradeep Deer, Daniel J. Shestowsky, William S. Kim, Do Geisbert, Joan B. Zeitlin, Larry Moyer, Crystal L. Roy, Chad J. Geisbert, Thomas W. Bornholdt, Zachary A. |
author_facet | Kuang, Erin Cross, Robert W. McCavitt-Malvido, Maria Abelson, Dafna M. Borisevich, Viktoriya Stuart, Lauren Agans, Krystle N. Mlakar, Neil Marimuthu, Arumugapradeep Deer, Daniel J. Shestowsky, William S. Kim, Do Geisbert, Joan B. Zeitlin, Larry Moyer, Crystal L. Roy, Chad J. Geisbert, Thomas W. Bornholdt, Zachary A. |
author_sort | Kuang, Erin |
collection | PubMed |
description | Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens associated with IV infusion and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a cocktail of two pan-ebolavirus mAbs, reverses the course of Sudan ebolavirus disease (Gulu variant) with a single IV or IM dose in non-human primates (NHPs) as late as five days post-exposure. We also investigate the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. When delivered as a post-exposure prophylactic or therapeutic, a single IM dose of MBP431 offered complete or significant protection in NHPs challenged with Zaire ebolavirus. In conjunction with previous studies, these results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known species of ebolavirus. |
format | Online Article Text |
id | pubmed-9228268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92282682022-06-25 Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic Kuang, Erin Cross, Robert W. McCavitt-Malvido, Maria Abelson, Dafna M. Borisevich, Viktoriya Stuart, Lauren Agans, Krystle N. Mlakar, Neil Marimuthu, Arumugapradeep Deer, Daniel J. Shestowsky, William S. Kim, Do Geisbert, Joan B. Zeitlin, Larry Moyer, Crystal L. Roy, Chad J. Geisbert, Thomas W. Bornholdt, Zachary A. Pathogens Article Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens associated with IV infusion and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a cocktail of two pan-ebolavirus mAbs, reverses the course of Sudan ebolavirus disease (Gulu variant) with a single IV or IM dose in non-human primates (NHPs) as late as five days post-exposure. We also investigate the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. When delivered as a post-exposure prophylactic or therapeutic, a single IM dose of MBP431 offered complete or significant protection in NHPs challenged with Zaire ebolavirus. In conjunction with previous studies, these results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known species of ebolavirus. MDPI 2022-06-07 /pmc/articles/PMC9228268/ /pubmed/35745509 http://dx.doi.org/10.3390/pathogens11060655 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kuang, Erin Cross, Robert W. McCavitt-Malvido, Maria Abelson, Dafna M. Borisevich, Viktoriya Stuart, Lauren Agans, Krystle N. Mlakar, Neil Marimuthu, Arumugapradeep Deer, Daniel J. Shestowsky, William S. Kim, Do Geisbert, Joan B. Zeitlin, Larry Moyer, Crystal L. Roy, Chad J. Geisbert, Thomas W. Bornholdt, Zachary A. Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title | Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title_full | Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title_fullStr | Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title_full_unstemmed | Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title_short | Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic |
title_sort | reversion of ebolavirus disease from a single intramuscular injection of a pan-ebolavirus immunotherapeutic |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228268/ https://www.ncbi.nlm.nih.gov/pubmed/35745509 http://dx.doi.org/10.3390/pathogens11060655 |
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