Post-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates

Nat Commun. 2019 Jan 10;10(1):105. doi: 10.1038/s41467-018-08040-w.

Abstract

The 2013-2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaviruses, Sudan (SUDV) and Bundibugyo (BDBV) viruses, as well as multiple variants of Marburg virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolavirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection. This cocktail when supplemented by the anti-MARV mAb MR191 exhibited 100% efficacy in MARV-infected NHPs. These findings provide a solid foundation for clinical development of broadly protective immunotherapeutics for use in future filovirus epidemics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use
  • Ebolavirus / classification
  • Ebolavirus / drug effects
  • Ebolavirus / immunology*
  • Ebolavirus / physiology
  • Filoviridae Infections / immunology*
  • Filoviridae Infections / therapy
  • Filoviridae Infections / virology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology
  • Immunotherapy / methods
  • Marburgvirus / drug effects
  • Marburgvirus / immunology*
  • Marburgvirus / physiology
  • Primate Diseases / immunology*
  • Primate Diseases / therapy
  • Primate Diseases / virology
  • Primates
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing