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Science 19 July 1996:
Vol. 273. no. 5273, pp. 352 - 354
DOI: 10.1126/science.273.5273.352
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Reports

Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization

Yukio Sato, Mark Roman, Helen Tighe, Delphine Lee, Maripat Corr, Minh-Duc Nguyen, Gregg J. Silverman, Martin Lotz, Dennis A. Carson, Eyal Raz *

Vaccination with naked DNA elicits cellular and humoral immune responses that have a T helper cell type 1 bias. However, plasmid vectors expressing large amounts of gene product do not necessarily induce immune responses to the encoded antigens. Instead, the immunogenicity of plasmid DNA (pDNA) requires short immunostimulatory DNA sequences (ISS) that contain a CpG dinucleotide in a particular base context. Human monocytes transfected with pDNA or double-stranded oligonucleotides containing the ISS, but not those transfected with ISS-deficient pDNA or oligonucleotides, transcribed large amounts of interferon-alpha , interferon-beta , and interleukin-12. Although ISS are necessary for gene vaccination, they down-regulate gene expression and thus may interfere with gene replacement therapy by inducing proinflammatory cytokines.

Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0663, USA.
* To whom correspondence should be addressed.


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C.-F. Hung, W.-F. Cheng, K.-F. Hsu, C.-Y. Chai, L. He, M. Ling, and T-C. Wu (2001)
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Differentiation of Murine NK Cells into Distinct Subsets Based on Variable Expression of the IL-12R{beta}2 Subunit.
H. Chakir, A. A. Camilucci, L. G. Filion, and J. R. Webb (2000)
J. Immunol. 165, 4985-4993
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Induction of Antitumor Immunity with Combination of HER2/neu DNA Vaccine and Interleukin 2 Gene-modified Tumor Vaccine.
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G. Wunderlich, I. C. Moura, and H. A. del Portillo (2000)
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Genetic Vaccination against Malaria Infection by Intradermal and Epidermal Injections of a Plasmid Containing the Gene Encoding the Plasmodium berghei Circumsporozoite Protein.
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The immunobiology and clinical potential of immunostimulatory CpG oligodeoxynucleotides.
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Effects of a Hexameric Deoxyriboguanosine Run Conjugation into CpG Oligodeoxynucleotides on Their Immunostimulatory Potentials.
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S. FUJIEDA, S. IHO, Y. KIMURA, H. YAMAMOTO, H. IGAWA, and H. SAITO (2000)
Am. J. Respir. Crit. Care Med. 162, 232-239
   Abstract »    Full Text »
Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion.
C. Vignes, E. Chiffoleau, P. Douillard, R. Josien, H. Peche, J.-M. Heslan, C. Usal, J.-P. Soulillou, and M. C. Cuturi (2000)
J. Immunol. 165, 96-101
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Genetic Immunization with Lung-Targeting Macroaggregated Polyethyleneimine-Albumin Conjugates Elicits Combined Systemic and Mucosal Immune Responses.
F. M. Orson, B. M. Kinsey, P. J. Hua, B. S. Bhogal, C. L. Densmore, and M. A. Barry (2000)
J. Immunol. 164, 6313-6321
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CpG motifs induce Langerhans cell migration in vivo.
E. Ban, L. Dupre, E. Hermann, W. Rohn, C. Vendeville, B. Quatannens, P. Ricciardi-Castagnoli, A. Capron, and G. Riveau (2000)
Int. Immunol. 12, 737-745
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Regulation of Murine Airway Eosinophilia and Th2 Cells by Antigen-Conjugated CpG Oligodeoxynucleotides as a Novel Antigen-Specific Immunomodulator.
H. Shirota, K. Sano, T. Kikuchi, G. Tamura, and K. Shirato (2000)
J. Immunol. 164, 5575-5582
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Suppression of Murine Cytomegalovirus (MCMV) Replication with a DNA Vaccine Encoding MCMV M84 (a Homolog of Human Cytomegalovirus pp65).
C. S. Morello, L. D. Cranmer, and D. H. Spector (2000)
J. Virol. 74, 3696-3708
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Ongoing Murine T1 or T2 Immune Responses to the Hepatitis B Surface Antigen Are Excluded from the Liver that Expresses Transgene-Encoded Hepatitis B Surface Antigen.
R. Schirmbeck, J. Wild, D. Stober, H. E. Blum, F. V. Chisari, M. Geissler, and J. Reimann (2000)
J. Immunol. 164, 4235-4243
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Regulation of T-helper Type 2 Cell and Airway Eosinophilia by Transmucosal Coadministration of Antigen and Oligodeoxynucleotides Containing CpG Motifs.