Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses

Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8(+) T cells induced by vaccinia virus immunization in a comparative...

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Bibliographic Details
Published in:The Journal of experimental medicine 2007-06, Vol.204 (6), p.1405-1416
Main Authors: Precopio, Melissa L, Betts, Michael R, Parrino, Janie, Price, David A, Gostick, Emma, Ambrozak, David R, Asher, Tedi E, Douek, Daniel C, Harari, Alexandre, Pantaleo, Giuseppe, Bailer, Robert, Graham, Barney S, Roederer, Mario, Koup, Richard A
Format: Article
Language:English
Subjects:
Adult
Amino Acid Sequence
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cytokines - metabolism
Flow Cytometry
Humans
Immunization
Immunophenotyping
Molecular Sequence Data
Smallpox Vaccine - immunology
Vaccinia virus - immunology
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Summary:Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8(+) T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus-specific CD8(+) T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon gamma, interleukin 2, macrophage inflammatory protein 1beta, and tumor necrosis factor alpha after antigenic stimulation. Responding CD8(+) T cells exhibited an unusual phenotype (CD45RO(-)CD27(intermediate)). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8(+) T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20062363