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Science 16 October 1998:
Vol. 282. no. 5388, pp. 476 - 480
DOI: 10.1126/science.282.5388.476
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Reports

Induction of Antigen-Specific Cytotoxic T Lymphocytes in Humans by a Malaria DNA Vaccine

Ruobing Wang, * Denise L. Doolan, * Thong P. Le, dagger Richard C. Hedstrom, Kevin M. Coonan, Yupin Charoenvit, Trevor R. Jones, Peter Hobart, Michal Margalith, Jennifer Ng, Walter R. Weiss, Martha Sedegah, Charles de Taisne, Jon A. Norman, Stephen L. Hoffman ddagger

CD8+ cytotoxic T lymphocytes (CTLs) are critical for protection against intracellular pathogens but often have been difficult to induce by subunit vaccines in animals. DNA vaccines elicit protective CD8+ T cell responses. Malaria-naïve volunteers who were vaccinated with plasmid DNA encoding a malaria protein developed antigen-specific, genetically restricted, CD8+ T cell-dependent CTLs. Responses were directed against all 10 peptides tested and were restricted by six human lymphocyte antigen (HLA) class I alleles. This first demonstration in healthy naïve humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs that were restricted by multiple HLA alleles in the same individual, provides a foundation for further human testing of this potentially revolutionary vaccine technology.

R. Wang, Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA, and Henry M. Jackson Foundation, Rockville, MD 20852, USA. D. L. Doolan, Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA, and Pan American Health Organization, Regional Office of the World Health Organization, Washington, DC 20037, USA. T. P. Le, R. C. Hedstrom, Y. Charoenvit, T. R. Jones, W. R. Weiss, M. Sedegah, S. L. Hoffman, Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA. K. M. Coonan, Medical Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21701, USA. P. Hobart, M. Margalith, J. A. Norman, Vical, San Diego, CA 92121, USA. J. Ng, C. W. Bill Young Department of Defense Bone Marrow Donor Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA. C. de Taisne, Pasteur-Merieux Connaught-France, 69007 Lyon, France.
*   These authors contributed equally to this work.

dagger    Present address: Clinical Research, Pasteur-Merieux Connaught-USA, Swiftwater, PA 18370, USA.

ddagger    To whom correspondence should be addressed. E-mail: hoffmans{at}nmripo.nmri.nnmc.navy.mil

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J. Virol. 75, 11457-11463
   Abstract »    Full Text »
Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines.
D. O'Hagan, M. Singh, M. Ugozzoli, C. Wild, S. Barnett, M. Chen, M. Schaefer, B. Doe, G. R. Otten, and J. B. Ulmer (2001)
J. Virol. 75, 9037-9043
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Multistage Multiantigen Heterologous Prime Boost Vaccine for Plasmodium knowlesi Malaria Provides Partial Protection in Rhesus Macaques.
W. O. Rogers, J. K. Baird, A. Kumar, J. A. Tine, W. Weiss, J. C. Aguiar, K. Gowda, R. Gwadz, S. Kumar, M. Gold, et al. (2001)
Infect. Immun. 69, 5565-5572
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Induction of CD4+ T cell-dependent CD8+ type 1 responses in humans by a malaria DNA vaccine.
R. Wang, J. Epstein, F. M. Baraceros, E. J. Gorak, Y. Charoenvit, D. J. Carucci, R. C. Hedstrom, N. Rahardjo, T. Gay, P. Hobart, et al. (2001)
PNAS
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CpG Oligodeoxynucleotides with Hepatitis B Surface Antigen (HBsAg) for Vaccination in HBsAg-Transgenic Mice.
E. Malanchere-Bres, P. J. Payette, M. Mancini, P. Tiollais, H. L. Davis, and M.-L. Michel (2001)
J. Virol. 75, 6482-6491
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Induction of a type 1 regulatory CD4 T cell response following V{beta}8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis.
V. Kumar, J. Maglione, J. Thatte, B. Pederson, E. Sercarz, and E. S. Ward (2001)
Int. Immunol. 13, 835-841
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Cancer Immunotherapy Using a DNA Vaccine Encoding the Translocation Domain of a Bacterial Toxin Linked to a Tumor Antigen.
C.-F. Hung, W.-F. Cheng, K.-F. Hsu, C.-Y. Chai, L. He, M. Ling, and T-C. Wu (2001)
Cancer Res. 61, 3698-3703
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HLA-A*01-Restricted Cytotoxic T-Lymphocyte Epitope from the Plasmodium falciparum Circumsporozoite Protein.
A. Kumar, S. Kumar, T. P. Le, S. Southwood, J. Sidney, J. Cohen, A. Sette, and S. L. Hoffman (2001)
Infect. Immun. 69, 2766-2771
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Intralymphatic immunization enhances DNA vaccination.
K. J. Maloy, I. Erdmann, V. Basch, S. Sierro, T. A. Kramps, R. M. Zinkernagel, S. Oehen, and T. M. Kündig (2001)
PNAS
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Prospects for Vaccines to Protect Against AIDS, Tuberculosis, and Malaria.
N. L. Letvin, B. R. Bloom, and S. L. Hoffman (2001)
JAMA 285, 606-611
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DNA vaccination: antigen presentation and the induction of immunity.
D. J. Shedlock and D. B. Weiner (2000)
J. Leukoc. Biol. 68, 793-806
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Induction of Vigorous Helper and Cytotoxic T Cell as well as B Cell Responses by Dendritic Cells Expressing a Modified Antigen Targeting Receptor-Mediated Internalization Pathway.
Z. You, X. F. Huang, J. Hester, L. Rollins, C. Rooney, and S.-Y. Chen (2000)
J. Immunol. 165, 4581-4591
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