title: Stat1-Deficient Mice Are Not an Appropriate Model for Efficacy Testing of Recombinant Vesicular Stomatitis Virus-Based Filovirus Vaccines.
abstract: Stat1(-/-) mice lack a response to interferon α, β, and γ, allowing for replication of nonadapted wild-type (wt) Ebolavirus and Marburgvirus. We sought to establish a mouse model for efficacy testing of live attenuated recombinant vesicular stomatitis virus (rVSV)-based filovirus vaccine vectors using wt Ebolavirus and Marburgvirus challenge strains. While infection of immunocompetent mice with different rVSV-based filovirus vectors did not cause disease, infection of Stat1(-/-) mice with the same vectors resulted in systemic infection and lethal outcome for the majority of tested rVSVs. Despite differences in viral loads, organ tropism was remarkably similar between rVSV filovirus vaccine vectors and rVSVwt, with the exception of the brain. In conclusion, Stat1(-/-) mice are not an appropriate immunocompromised mouse model for efficacy testing of live attenuated, replication-competent rVSV vaccine vectors.
authors.affiliation: Laboratory of Virology.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kercher
authors.affiliation: Laboratory of Virology Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula.
authors.forename: Joshua
authors.initials: J
authors.lastname: Marceau
authors.affiliation: Laboratory of Virology.
authors.forename: Anthony
authors.initials: A
authors.lastname: York
authors.affiliation: Laboratory of Virology.
authors.forename: Julie
authors.initials: J
authors.lastname: Callsion
authors.affiliation: Rocky Mountain Veterinary Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
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: Laboratory of Virology.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology; D016563:Filoviridae / Q000276:immunology*; D018702:Filoviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D019142:Hemorrhagic Fever, Ebola / Q000235:genetics / Q000276:immunology / Q000821:virology; D008379:Marburg Virus Disease / Q000235:genetics / Q000276:immunology / Q000821:virology; D029024:Marburgvirus / Q000276:immunology; D051379:Mice; D050794:STAT1 Transcription Factor / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology*; D014709:Vero Cells; D054243:Vesicular Stomatitis / Q000276:immunology*; D019562:Viral Load / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Ebolavirus; Marburgvirus; Stat1-deficient mice; Vesicular stomatitis virus; vaccine