Protective cytotoxic T-cell responses induced by venezuelan equine encephalitis virus replicons expressing Ebola virus proteins.
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.
Olinger
Gene G
GG
United States Army Medical Research Institute of Infectious Diseases, Division of Virology, 1425 Porter Street, Frederick, MD 21702-5011, USA.
Bailey
Michael A
MA
Dye
John M
JM
Bakken
Russell
R
Kuehne
Ana
A
Kondig
John
J
Wilson
Julie
J
Hogan
Robert J
RJ
Hart
Mary Kate
MK
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
D000939:Epitopes; D010446:Peptide Fragments; D014764:Viral Proteins; D014765:Viral Vaccines