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*
Wisconsin Regional Primate Research Center and
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53715;
PowderJect, Inc., Madison, WI 53711;
§
Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
¶
Epimmune, Inc., San Diego, CA 92121;
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Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322; and
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Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
The observed role of CTL in the containment of AIDS virus
replication suggests that an effective HIV vaccine will be required to
generate strong CTL responses. Because epitope-based vaccines offer
several potential advantages for inducing strong, multispecific CTL
responses, we tested the ability of an epitope-based DNA prime/modified
vaccinia virus Ankara (MVA) boost vaccine to induce CTL responses
against a single SIVgag CTL epitope. As assessed using both
51Cr release assays and tetramer staining of in vitro
stimulated PBMC, DNA vaccinations administered to the skin with the
gene gun induced and progressively increased p11C, C
M
(CTPYDINQM)-specific CD8+ T lymphocyte responses in six of
six Mamu-A*01+ rhesus macaques. Tetramer
staining of fresh, unstimulated PBMC from two of the DNA-vaccinated
animals indicated that as much as 0.4% of all
CD3+/CD8
+ T lymphocytes were specific for
the SIVgag CTL epitope. Administration of MVA expressing the SIVgag CTL
epitope further boosted these responses, such that 0.8–20.0% of
CD3+/CD8+ T lymphocytes in fresh,
unstimulated PBMC were now Ag specific. Enzyme-linked immunospot assays
confirmed this high frequency of Ag-specific cells, and intracellular
IFN-
staining demonstrated that the majority of these cells produced
IFN- after peptide stimulation. Moreover, direct ex vivo
SIV-specific cytotoxic activity could be detected in PBMC from five of
the six DNA/MVA-vaccinated animals, indicating that this epitope-based
DNA prime/MVA boost regimen represents a potent method for inducing
high levels of functionally active, Ag-specific CD8+ T
lymphocytes in non-human primates.
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H. Horton, T. U. Vogel, D. K. Carter, K. Vielhuber, D. H. Fuller, T. Shipley, J. T. Fuller, K. J. Kunstman, G. Sutter, D. C. Montefiori, et al. Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239 J. Virol., June 14, 2002; 76(14): 7187 - 7202. [Abstract] [Full Text] [PDF]
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T. M. Allen, L. Mortara, B. R. Mothe, M. Liebl, P. Jing, B. Calore, M. Piekarczyk, R. Ruddersdorf, D. H. O'Connor, X. Wang, et al. Tat-Vaccinated Macaques Do Not Control Simian Immunodeficiency Virus SIVmac239 Replication J. Virol., March 19, 2002; 76(8): 4108 - 4112. [Abstract] [Full Text] [PDF]
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Z. Hel, W.-P. Tsai, A. Thornton, J. Nacsa, L. Giuliani, E. Tryniszewska, M. Poudyal, D. Venzon, X. Wang, J. Altman, et al. Potentiation of Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cell Responses by a DNA-SIV and NYVAC-SIV Prime/Boost Regimen J. Immunol., December 15, 2001; 167(12): 7180 - 7191. [Abstract] [Full Text] [PDF]
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 W. S. Meng, L. H. Butterfield, A. Ribas, V. B. Dissette, J. B. Heller, G. A. Miranda, J. A. Glaspy, W. H. McBride, and J. S. Economou {alpha}-Fetoprotein-specific Tumor Immunity Induced by Plasmid Prime-Adenovirus Boost Genetic Vaccination Cancer Res., December 1, 2001; 61(24): 8782 - 8786. [Abstract] [Full Text] [PDF]
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R. S. Veazey, M.-C. Gauduin, K. G. Mansfield, I. C. Tham, J. D. Altman, J. D. Lifson, A. A. Lackner, and R. P. Johnson Emergence and Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells in the Intestines of Macaques during Primary Infection J. Virol., November 1, 2001; 75(21): 10515 - 10519. [Abstract] [Full Text] [PDF]
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R. Maile, B. Wang, W. Schooler, A. Meyer, E. J. Collins, and J. A. Frelinger Antigen-Specific Modulation of an Immune Response by In Vivo Administration of Soluble MHC Class I Tetramers J. Immunol., October 1, 2001; 167(7): 3708 - 3714. [Abstract] [Full Text] [PDF]
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D. H. Barouch, S. Santra, M. J. Kuroda, J. E. Schmitz, R. Plishka, A. Buckler-White, A. E. Gaitan, R. Zin, J.-H. Nam, L. S. Wyatt, et al. Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination J. Virol., June 1, 2001; 75(11): 5151 - 5158. [Abstract] [Full Text]
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M. K. Slifka, R. Pagarigan, I. Mena, R. Feuer, and J. L. Whitton Using Recombinant Coxsackievirus B3 To Evaluate the Induction and Protective Efficacy of CD8+ T Cells during Picornavirus Infection J. Virol., March 1, 2001; 75(5): 2377 - 2387. [Abstract] [Full Text]
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T. U. Vogel, T. M. Allen, J. D. Altman, and D. I. Watkins Functional Impairment of Simian Immunodeficiency Virus-Specific CD8+ T Cells during the Chronic Phase of Infection J. Virol., March 1, 2001; 75(5): 2458 - 2461. [Abstract] [Full Text]
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T. M. Allen, B. R. Mothé, J. Sidney, P. Jing, J. L. Dzuris, M. E. Liebl, T. U. Vogel, D. H. O'Connor, X. Wang, M. C. Wussow, et al. CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing J. Virol., January 15, 2001; 75(2): 738 - 749. [Abstract] [Full Text]
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 D. H. Barouch, S. Santra, J. E. Schmitz, M. J. Kuroda, T.-M. Fu, W. Wagner, M. Bilska, A. Craiu, X. X. Zheng, G. R. Krivulka, et al. Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination Science, October 20, 2000; 290(5491): 486 - 492. [Abstract] [Full Text]
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M. A. Cromwell, R. S. Veazey, J. D. Altman, K. G. Mansfield, R. Glickman, T. M. Allen, D. I. Watkins, A. A. Lackner, and R. P. Johnson Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus J. Virol., September 15, 2000; 74(18): 8762 - 8766. [Abstract] [Full Text]
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D. T. Evans, P. Jing, T. M. Allen, D. H. O'Connor, H. Horton, J. E. Venham, M. Piekarczyk, J. Dzuris, M. Dykhuzen, J. Mitchen, et al. Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression J. Virol., August 15, 2000; 74(16): 7400 - 7410. [Abstract] [Full Text]
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