title: Protective cytotoxic T-cell responses induced by venezuelan equine encephalitis virus replicons expressing Ebola virus proteins.
abstract: Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that antibody-mediated protection could only be demonstrated after vaccination against the glycoprotein. In this study, the murine CD8(+) T-cell responses to six Ebola virus proteins were examined. CD8(+) T cells specific for Ebola virus glycoprotein, nucleoprotein, and viral proteins (VP24, VP30, VP35, and VP40) were identified by intracellular cytokine assays using splenocytes from vaccinated mice. The cells were expanded by restimulation with peptides and demonstrated cytolytic activity. Adoptive transfer of the CD8(+) cytotoxic T cells protected filovirus naïve mice from challenge with Ebola virus. These data support a role for CD8(+) cytotoxic T cells as part of a protective mechanism induced by vaccination against six Ebola virus proteins and provide additional evidence that cytotoxic T-cell responses can contribute to protection from filovirus infections.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Division of Virology, 1425 Porter Street, Frederick, MD 21702-5011, USA.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Olinger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bailey
authors.forename: John M
authors.initials: JM
authors.lastname: Dye
authors.forename: Russell
authors.initials: R
authors.lastname: Bakken
authors.forename: Ana
authors.initials: A
authors.lastname: Kuehne
authors.forename: John
authors.initials: J
authors.lastname: Kondig
authors.forename: Julie
authors.initials: J
authors.lastname: Wilson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hogan
authors.forename: Mary Kate
authors.initials: MK
authors.lastname: Hart
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology*; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology; D000939:Epitopes / Q000737:chemistry; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D012093:Replicon / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D014764:Viral Proteins; D014765:Viral Vaccines