title: An Inactivated Rabies Virus-Based Ebola Vaccine, FILORAB1, Adjuvanted With Glucopyranosyl Lipid A in Stable Emulsion Confers Complete Protection in Nonhuman Primate Challenge Models.
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.
authors.affiliation: Emerging Viral Pathogens Section.
authors.forename: Reed F
authors.initials: RF
authors.lastname: Johnson
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College.
authors.forename: Drishya
authors.initials: D
authors.lastname: Kurup
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Maryland.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Hagen
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College.
authors.forename: Christine
authors.initials: C
authors.lastname: Fisher
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College.
authors.forename: Rohan
authors.initials: R
authors.lastname: Keshwara
authors.affiliation: Emerging Viral Pathogens Section.
authors.forename: Amy
authors.initials: A
authors.lastname: Papaneri
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Maryland.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Perry
authors.affiliation: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Maryland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Cooper
authors.affiliation: Emerging Viral Pathogens Section Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Maryland.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.affiliation: Genetic Sciences, Thermo Fisher Scientific.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Immune Design, South San Francisco, California Immune Design, Seattle, Washington.
authors.forename: Jan
authors.initials: J
authors.lastname: Ter Meulen
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wirblich
authors.affiliation: Department of Microbiology and Immunology, Sidney Kimmel Medical College Jefferson Vaccine Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D046129:Ebola Vaccines / Q000276:immunology*; D029043:Ebolavirus / Q000276:immunology*; D004655:Emulsions; D005260:Female; D005960:Glucosides / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008050:Lipid A / Q000276:immunology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011818:Rabies / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011819:Rabies Vaccines / Q000276:immunology; D011820:Rabies virus / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D046129:Ebola Vaccines; D004655:Emulsions; D005960:Glucosides; D008050:Lipid A; D011819:Rabies Vaccines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D015164:Vaccines, Inactivated; D014614:Vaccines, Synthetic; C000608161:glucopyranosyl lipid-A
keywords: Ebola; GLA-SE; challenge model; nonhuman primate; protection; rabies; vaccine