Development of Antigen-Specific Memory CD8⁺ T Cells Following Live-Attenuated Chimeric West Nile Virus Vaccination

• Published in: The Journal of infectious diseases Vol. 203; no. 4; pp. 513 - 522
• Main Authors: Smith, Heidi L., Monath, Thomas P., Pazoles, Pamela, Rothman, Alan L., Casey, Diane M., Terajima, Masanori, Ennis, Francis A., Guirakhoo, Farshad, Green, Sharone
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.02.2011
• Subjects: Antigens, Viral - immunology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Chemokine CCL4 - secretion; Cytokines; Epitopes; Epitopes, T-Lymphocyte - immunology; Fundamental and applied biological sciences. Psychology; Human Experimentation; Humans; Immunization; Immunologic Memory; Infections; Infectious diseases; Interferon-gamma - secretion; Major and Brief Reports; Medical sciences; Memory; Microbiology; Miscellaneous; Placebos - administration & dosage; T lymphocytes; T-Lymphocyte Subsets - immunology; Tumor Necrosis Factor-alpha - secretion; Vaccination; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Viral Envelope Proteins - immunology; Viremia; Virology; Viruses; West Nile virus; West Nile virus - immunology; West Nile Virus Vaccines - administration & dosage; West Nile Virus Vaccines - immunology; Virus; Antigen; Infection; Pathogenic; Vaccination; West Nile virus; Japanese encephalitis group virus; Flaviviridae; Attenuated strain; Flavivirus; CD8 T lymphocyte
• ISSN: 0022-1899; 1537-6613; 1537-6613; 0022-1899
• DOI: 10.1093/infdis/jiq074

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 1β, 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.