title: Replication-deficient ebolavirus as a vaccine candidate.
abstract: Ebolavirus causes severe hemorrhagic fever, with case fatality rates as high as 90%. Currently, no licensed vaccine is available against Ebolavirus. We previously generated a replication-deficient, biologically contained Ebolavirus, EbolaDeltaVP30, which lacks the essential VP30 gene, grows only in cells stably expressing this gene product, and is genetically stable. Here, we evaluated the vaccine potential of EbolaDeltaVP30. First, we demonstrated its safety in STAT-1-knockout mice, a susceptible animal model for Ebolavirus infection. We then tested its protective efficacy in two animal models, mice and guinea pigs. Mice immunized twice with EbolaDeltaVP30 were protected from a lethal infection of mouse-adapted Ebolavirus. Virus titers in the serum of vaccinated mice were significantly lower than those in nonvaccinated mice. Protection of mice immunized with EbolaDeltaVP30 was associated with a high antibody response to the Ebolavirus glycoprotein and the generation of an Ebolavirus NP-specific CD8(+) T-cell response. Guinea pigs immunized twice with EbolaDeltaVP30 were also protected from a lethal infection of guinea pig-adapted Ebolavirus. Our study demonstrates the potential of the EbolaDeltaVP30 virus as a new vaccine platform.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Halfmann
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hatta
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Suresh
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D046129:Ebola Vaccines / Q000235:genetics / Q000276:immunology*; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D020043:Genes, Essential; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000517:prevention & control*; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000172:deficiency; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*; D014766:Viremia / Q000517:prevention & control; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D046129:Ebola Vaccines; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D014157:Transcription Factors; C479897:VP30 protein, ebola virus; D014764:Viral Proteins