An Inactivated Rabies Virus-Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models

J Infect Dis. 2016 Oct 15;214(suppl 3):S342-S354. doi: 10.1093/infdis/jiw231. Epub 2016 Jul 24.

Abstract

The 2013-2016 West African Ebola virus (EBOV) disease outbreak was the largest filovirus outbreak to date. Over 28 000 suspected, probable, or confirmed cases have been reported, with a 53% case-fatality rate. The magnitude and international impact of this EBOV outbreak has highlighted the urgent need for a safe and efficient EBOV vaccine. To this end, we demonstrate the immunogenicity and protective efficacy of FILORAB1, a recombinant, bivalent, inactivated rabies virus-based EBOV vaccine, in rhesus and cynomolgus monkeys. Our results demonstrate that the use of the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid A in stable emulsion (GLA-SE) as an adjuvant increased the efficacy of FILORAB1 to 100% protection against lethal EBOV challenge, with no to mild clinical signs of disease. Furthermore, all vaccinated subjects developed protective anti-rabies virus antibody titers. Taken together, these results support further development of FILORAB1/GLA-SE as an effective preexposure EBOV vaccine.

Keywords: Ebola; GLA-SE; challenge model; nonhuman primate; protection; rabies; vaccine.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral / immunology
  • Ebola Vaccines / immunology*
  • Ebolavirus / immunology*
  • Emulsions
  • Female
  • Glucosides / immunology*
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / prevention & control*
  • Hemorrhagic Fever, Ebola / virology
  • Lipid A / immunology*
  • Macaca fascicularis
  • Macaca mulatta
  • Male
  • Rabies / immunology
  • Rabies / prevention & control*
  • Rabies / virology
  • Rabies Vaccines / immunology
  • Rabies virus / immunology*
  • Toll-Like Receptor 4 / immunology
  • Vaccines, Inactivated / immunology
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Ebola Vaccines
  • Emulsions
  • Glucosides
  • Lipid A
  • Rabies Vaccines
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Vaccines, Inactivated
  • Vaccines, Synthetic
  • glucopyranosyl lipid-A