title: Development of antigen-specific memory CD8+ T cells following live-attenuated chimeric West Nile virus vaccination.
abstract: ChimeriVax-WN02 is a novel live-attenuated West Nile virus (WNV) vaccine containing modified WNV premembrane (prM) and envelope (E) sequences inserted into the yellow fever 17D vaccine genome. We investigated the induction and evolution of CD8(+) T cell responses to a WNV envelope epitope, which is a dominant target in naturally infected HLA-A*02-positive individuals. WNV epitope-specific CD8(+) T cells were detected by HLA tetramer staining in 22 of 23 donors tested, with peak frequencies occurring between days 14 and 28. WNV epitope-specific T cells evolved from an effector phenotype to a long-lived memory phenotype. In the majority of donors, CD8(+) T cells were able to lyse targets expressing WNV envelope protein and produced macrophage inflammatory protein 1ß, interferon γ, and/or tumor necrosis factor α following envelope peptide stimulation. WNV E-specific CD8(+) T cell responses were detected for up to 1 year after vaccination. The evolution of this WNV-specific T cell response is similar to that observed in established, highly immunogenic vaccines.
authors.affiliation: Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Smith
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Pamela
authors.initials: P
authors.lastname: Pazoles
authors.forename: Alan L
authors.initials: AL
authors.lastname: Rothman
authors.forename: Diane M
authors.initials: DM
authors.lastname: Casey
authors.forename: Masanori
authors.initials: M
authors.lastname: Terajima
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4 / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006805:Human Experimentation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D010919:Placebos / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; C066507:CCL4 protein, human; D054407:Chemokine CCL4; C445780:ChimeriVax; D018984:Epitopes, T-Lymphocyte; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines; D007371:Interferon-gamma