Abstract
Immunization with plasmid DNA (pDNA) results in potent humoral and cellular immune responses that are specific to the expressed antigen. Intradermal injection of plasmid DNA (pDNA) in normal saline induces T helper cell differentiation to the T helper 1 type (Th1). This response is characterized by high levels of interferon (IFNy) and the production of Isotype G2a antibodies, as well as the activation of strong major histocompatibility complex (MHC) class I-restricted cytotoxic T-lymphocyte responses (1–5). Additionally, immunization with plasmid DNA can dictate the dominant phenotype of the overall response. Not only can an antigen-specific Th2 response be switched to an antigen-specific Th 1 response by plasmid DNA immunization, but the Th 1 response induced by pDNA immunization also prevails over a later attempt to induce a Th2 response by protein in alum immunization (2). This bias in the T-cell cytokine profile and the potent response relative to the quantitatively small amount of protein produced by the pDNA injection suggested that the DNA was acting as an adjuvant to enhance the response.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Manickan, E., Rouse, R. J., Yu, Z., Wire, W. S. and Rouse, B. T. (1995) Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes, J. Immunol. 155, 259–265.
Raz, E., Tighe, H., Sato, Y., et al. (1996) Preferential induction of a Th l immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization. Proc. Natl. Acad. Sci. USA, 93, 5141–5145.
Feltquate, D. M., Heaney, S., Webster, R. G. and Robinson, H. L. (1997) Different T helper cell types and antibody isotypes generated by saline and gene gun DNA immunization. J. Immunol. 158, 2278–2284.
Ulmer, J. B., Donnelly, J. J., Parker, S. E., et al. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein, Science 259, 1745–1749.
Davis, H. L., Schirmbeck, R., Reimann, J. and Whalen, R. G. (1995) DNAmediated immunization in mice induces a potent MHC class I-restricted cytotoxic T lymphocyte response to the hepatitis B envelope protein. Hum. Gene Ther. 6, 1447–1456.
Klinman, D. M., Yamshchikov, G. and Ishigatsubo, Y. (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158, 3635–3639.
Sato, Y., Roman, M., Tighe, H., et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273, 352–354.
Shimada, S., Yano, O., Inoue, H., et al. (1985) Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors. J. Natl. Cancer Inst. 74, 681–688.
Tokunaga, T., Yamamoto, H., Shimada, S., et al. (1984) Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity. J. Natl. Cancer Inst. 72, 955–962.
Shimada, S., Yano, O., and Tokunaga, T. (1986) In vivo augmentation of natural killer cell activity with a deoxyribonucleic acid fraction of BCG. Jpn. J. Cancer Res. 77, 808–816.
Yamamoto, S., Kuramoto, E., Shimada, S., and Tokunaga, T. (1988) In vitro augmentation of natural killer cell activity and production of interferon-alpha/ beta and -gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG. Jpn. J. Cancer Res. 79, 866–873.
Kuramoto, E., Yano, O., Kimura, Y., et al. (1992) Oligonucleotide sequences required for natural killer cell activation. Jpn. J. Cancer Res. 83, 1128–1131.
Tokunaga, T., Yano, O., Kuramoto, E., et al. (1992) Synthetic oligonucleotides with particular base sequences from the cDNA encoding proteins of Mycobacterium bovis BCG induce interferons and activate natural killer cells. Microbiol. Immunol. 36, 55–66.
Yamamoto, S., Yamamoto, T., Kataoka, T., Kuramoto, E., Yano, O., and Tokunaga, T. (1992) Unique palindromic sequences in synthetic oligonucleotides are required to induce IFN [correction of INF] and augment IFN-mediated [correction of INF] natural killer activity. J. Immunol. 148, 4072–4076.
Wolff, J. A., Malone, R. W., Williams, P., et al. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468.
Roman, M., Martin-Orozco, E., Goodman, J. S., et al. (1997) Immunostimulatory DNA sequences function as T helper- 1-promoting adj uvants. Nat. Med. 3, 849–854.
Chu, R. S., Targoni, O. S., Krieg, A. M., Lehmann, P. V., and Harding, C. V. (1997) CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th 1) immunity, J. Exp. Med. 186, 1623–1631.
Tighe, H., Takabayashi, K., Schwartz, D., et al. (2000) Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity. Eur. J. Immunol. 30, 1939–1947.
Cho, H. J., Takabayashi, K., Cheng, P. M., et al. (2000) Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cellindependent mechanism. Nat. Biotechnol. 18, 509–514.
Krieg, A. M., Yi, A. K., Matson, S., et al. (1995) CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374, 546–549.
Liang, H., Nishioka, Y., Reich, C. F., Pisetsky, D. S., and Lipsky, P. E. (1996) Activation of human B cells by phosphorothioate oligodeoxynucleotides. J. Clin. Invest. 98, 1119–1129.
Branda, R. F., Moore, A. L., Lafayette, A. R., et al. (1996) Amplification of antibody production by phosphorothioate oligodeoxynucleotides. J. Lab. Clin. Med. 128, 329–338.
Monteith, D. K., Henry, S. P., Howard, R. B., et al. (1997) Immune stimulation a class effect of phosphorothioate oligodeoxynucleotides in rodents. Anticancer Drug Des. 12, 421–432.
Verthelyi, D., Ishii, K., Gursel, M., Takeshita, F., and Klinman, D. (2001) Human peripheral blood cells differentially recognize and respond to two distinct CPG motifs. J. Immunol. 166, 2372–2377.
Ballas, Z. K., Rasmussen, W. L., and Krieg, A. M. (1996) Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J. Immunol. 157, 1840–1845.
Yamamoto, T., Yamamoto, S., Kataoka, T., and Tokunaga, T. (1994) Ability of oligonucleotides with certain palindromes to induce interferon production and augment natural killer cell activity is associated with their base length. Antisense Res. Dey. 4, 119–122.
Krieg, A. M., Wu, T., Weeratna, R., et al. (1998) Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs. Proc. Natl. Acad. Sci. USA 95, 12,631–12,636.
Martin-Orozco, E., Kobayashi, H., Van Uden, J., Nguyen, M., Kornbluth, R. S., and Raz, E. (1999) Enhancement of antigen-presenting cell surface molecules involved in cognate interactions by immunostimulatory DNA sequences Int. Immunol. 11, 1111–1113.
Sun, S., Zhang, X., Tough, D. F., and Sprent, J. (1998) Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med. 188, 2335–2342.
Brinkmann, V., Geiger, T., Alkan, S., and Heusser, C. H. (1993) Interferon alpha increases the frequency of interferon gamma-producing human CD4+ T cells. J. Exp. Med. 178, 1655–1663.
Yaegashi, Y., Nielsen, P., Sing, A., Galanos, C., and Freudenberg, M. A. (1995) Interferon beta, a cofactor in the interferon gamma production induced by gram-negative bacteria in mice. J. Exp. Med. 181, 953–960.
Trinchieri, G. (1995) Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu. Rev. Immunol. 13, 251–276.
Okamura, H., Tsutsi, H., Komatsu, T., et al. (1995) Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 378, 88–91.
Yi, A. K., Chace, J. H., Cowdery, J. S., and Krieg, A. M. (1996) IFN-gamma promotes IL-6 and IgM secretion in response to CpG motifs in bacterial DNA and oligodeoxynucleotides. J. Immunol. 156, 558–564.
Yi, A. K., Klinman, D. M., Martin, T. L., Matson, S. and Krieg, A. M. (1996) Rapid immune activation by CpG motifs in bacterial DNA. Systemic induction of IL-6 transcription through an antioxidant-sensitive pathway. J. Immunol. 157, 5394–5402.
Schwartz, D. A., Quinn, T. J., Thorne, P. S., Sayeed, S., Yi, A. K., and Krieg, A. M. (1997) CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract. J. Clin. Invest. 100, 68–73.
Akbari, O., Panjwani, N., Garcia, S., Tascon, R., Lowrie, D., and Stockinger, B. (1999) DNA vaccination: transfection and activation of dendritic cells as key events for immunity, J. Exp. Med. 189, 169–718.
Chan, K., Lee, D. J., Schubert, A., et al. (2001) The roles of MHC class II, CD40, and B7 costimulation in CTL induction by plasmid DNA, J. Immunol. 166, 3061–3066.
Casares, S., Inaba, K., Brumeanu, T. D., Steinman, R. M., and Bona, C. A. (1997) Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope. J. Exp. Med. 186, 1481–1486.
Porgador, A., Irvine, K. R., Iwasaki, A., Barber, B. H., Restifo, N. P., and Germain, R. N. (1998) Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization, J. Exp. Med. 188, 1075–1082.
Condon, C., Watkins, S. C., Celluzzi, C. M., Thompson, K.m and Falo, L. D., Jr. (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat. Med. 2, 1122–1128.
Hemmi, H., Takeuchi, O., Kawai, T., et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740–745.
Yi, A. K. and Krieg, A. M. (1998) CpG DNA rescue from anti-IgM-induced WEHI-231 B lymphoma apoptosis via modulation of I kappa B alpha and I kappa B beta and sustained activation of nuclear factor-kappa B/c-Rel, J. Immunol. 160, 1240–1245.
Chu, W., Gong, X., Li, Z., et al. (2000) DNA-PKcs is required for activation of innate immunity by immunostimulatory DNA. Cell 103, 909–918.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Wu, C.C.N., Tang, C.M., Crain, B., Corr, M. (2002). Immunostimulatory Sequences in Plasmid Vectors. In: Raz, E. (eds) Microbial DNA and Host Immunity. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-305-7_17
Download citation
DOI: https://doi.org/10.1007/978-1-59259-305-7_17
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4684-9728-1
Online ISBN: 978-1-59259-305-7
eBook Packages: Springer Book Archive