title: Vaccination With a Highly Attenuated Recombinant Vesicular Stomatitis Virus Vector Protects Against Challenge With a Lethal Dose of Ebola Virus.
abstract: Previously, recombinant vesicular stomatitis virus (rVSV) pseudotypes expressing Ebolavirus glycoproteins (GPs) in place of the VSV G protein demonstrated protection of nonhuman primates from lethal homologous Ebolavirus challenge. Those pseudotype vectors contained no additional attenuating mutations in the rVSV genome. Here we describe rVSV vectors containing a full complement of VSV genes and expressing the Ebola virus (EBOV) GP from an additional transcription unit. These rVSV vectors contain the same combination of attenuating mutations used previously in the clinical development pathway of an rVSV/human immunodeficiency virus type 1 vaccine. One of these rVSV vectors (N4CT1-EBOVGP1), which expresses membrane-anchored EBOV GP from the first position in the genome (GP1), elicited a balanced cellular and humoral GP-specific immune response in mice. Guinea pigs immunized with a single dose of this vector were protected from any signs of disease following lethal EBOV challenge, while control animals died in 7-9 days. Subsequently, N4CT1-EBOVGP1 demonstrated complete, single-dose protection of 2 macaques following lethal EBOV challenge. A single sham-vaccinated macaque died from disease due to EBOV infection. These results demonstrate that highly attenuated rVSV vectors expressing EBOV GP may provide safer alternatives to current EBOV vaccines.
authors.affiliation: Department of Virology and Vaccine Vectors.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Matassov
authors.affiliation: Laboratory of Virology.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.affiliation: Department of Virology and Vaccine Vectors.
authors.forename: Terri
authors.initials: T
authors.lastname: Latham
authors.affiliation: Department of Immunology, Profectus BioSciences, Tarrytown, New York.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Immunology, Profectus BioSciences, Tarrytown, New York.
authors.forename: Ayuko
authors.initials: A
authors.lastname: Ota-Setlik
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.affiliation: Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.affiliation: Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Mire
authors.affiliation: Department of Virology and Vaccine Vectors.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hamm
authors.affiliation: Department of Virology and Vaccine Vectors.
authors.forename: Becky
authors.initials: B
authors.lastname: Nowak
authors.affiliation: Department of Immunology, Profectus BioSciences, Tarrytown, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.affiliation: Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.affiliation: Department of Virology and Vaccine Vectors Department of Immunology, Profectus BioSciences, Tarrytown, New York.
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.affiliation: Laboratory of Virology.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Department of Virology and Vaccine Vectors.
authors.forename: David K
authors.initials: DK
authors.lastname: Clarke
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D029043:Ebolavirus / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000821:virology; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000276:immunology*; D054243:Vesicular Stomatitis / Q000276:immunology; D018116:Vesiculovirus / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D014613:Vaccines, Attenuated; D014764:Viral Proteins; D014765:Viral Vaccines
keywords: Ebola vaccine; attenuation; challenge; glycoprotein; nonhuman primates; rVSV vector