Pan-ebolavirus protective therapy by two multifunctional human antibodies

Pavlo Gilchuk, Charles D. Murin, Robert W. Cross, Philipp A. Ilinykh, Kai Huang, Natalia Kuzmina, Viktoriya Borisevich, Krystle N. Agans, Joan B. Geisbert, Seth J. Zost, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Robin G. Bombardi, Robert H. Carnahan, Alexander Bukreyev, Thomas W. Geisbert, Andrew B. Ward, James E. Crowe

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Ebolaviruses cause a severe and often fatal illness with the potential for global spread. Monoclonal antibody-based treatments that have become available recently have a narrow therapeutic spectrum and are ineffective against ebolaviruses other than Ebola virus (EBOV), including medically important Bundibugyo (BDBV) and Sudan (SUDV) viruses. Here, we report the development of a therapeutic cocktail comprising two broadly neutralizing human antibodies, rEBOV-515 and rEBOV-442, that recognize non-overlapping sites on the ebolavirus glycoprotein (GP). Antibodies in the cocktail exhibited synergistic neutralizing activity, resisted viral escape, and possessed differing requirements for their Fc-regions for optimal in vivo activities. The cocktail protected non-human primates from ebolavirus disease caused by EBOV, BDBV, or SUDV with high therapeutic effectiveness. High-resolution structures of the cocktail antibodies in complex with GP revealed the molecular determinants for neutralization breadth and potency. This study provides advanced preclinical data to support clinical development of this cocktail for pan-ebolavirus therapy.

Original languageEnglish (US)
Pages (from-to)5593-5607.e18
JournalCell
Volume184
Issue number22
DOIs
StatePublished - Oct 28 2021

Keywords

  • Ebolavirus
  • antibody therapeutics
  • ebolavirus infection
  • epitope mapping
  • glycoprotein
  • neutralizing antibodies
  • viral antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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