The Journal of Experimental Medicine
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Published online May 29, 2007
doi:10.1084/jem.20062363
The Journal of Experimental Medicine, Vol. 204, No. 6, 1405-1416
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Precopio et al.
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ARTICLE

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

Melissa L. Precopio1, Michael R. Betts6, Janie Parrino2, David A. Price3,7, Emma Gostick7, David R. Ambrozak1, Tedi E. Asher3, Daniel C. Douek3, Alexandre Harari8, Giuseppe Pantaleo8, Robert Bailer4, Barney S. Graham2, Mario Roederer5, and Richard A. Koup1

1 Immunology Laboratory, 2 Viral Pathogenesis Laboratory, 3 Human Immunology Section, 4 Immunology Core Laboratory, 5 ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
6 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104
7 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, England, UK
8 Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland

CORRESPONDENCE Richard A. Koup: rkoup{at}mail.nih.gov

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 1ß, and tumor necrosis factor {alpha} after antigenic stimulation. Responding CD8+ T cells exhibited an unusual phenotype (CD45ROCD27intermediate). 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.


Abbreviations used: APC, allophycocyanin; CCR, CC chemokine receptor; MFI, median fluorescence intensity; MIP, macrophage inflammatory protein; MVA, modified vaccinia virus Ankara.


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