Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic

Erin Kuang, Robert W. Cross, Maria McCavitt-Malvido, Dafna M. Abelson, Viktoriya Borisevich, Lauren Stuart, Krystle N. Agans, Neil Mlakar, Arumugapradeep Marimuthu, Daniel J. Deer, William S. Shestowsky, Do Kim, Joan B. Geisbert, Larry Zeitlin, Crystal L. Moyer, Chad J. Roy, Thomas W. Geisbert, Zachary A. Bornholdt

Research output: Contribution to journalArticlepeer-review

Abstract

Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be chal-lenging, 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 nonhuman 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.

Original languageEnglish (US)
Article number655
JournalPathogens
Volume11
Issue number6
DOIs
StatePublished - Jun 2022

Keywords

  • EBOV
  • MBP134
  • SUDV
  • Sudan
  • anti-viral
  • immunotherapeutic
  • injection
  • intramuscular
  • pan-ebolavirus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • General Immunology and Microbiology
  • Microbiology (medical)
  • Infectious Diseases

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