Skip to main content

Immunostimulatory Sequences in Plasmid Vectors

  • Chapter
  • 262 Accesses

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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.

    PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. Klinman, D. M., Yamshchikov, G. and Ishigatsubo, Y. (1997) Contribution of CpG motifs to the immunogenicity of DNA vaccines. J. Immunol. 158, 3635–3639.

    PubMed  CAS  Google Scholar 

  7. Sato, Y., Roman, M., Tighe, H., et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273, 352–354.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. 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.

    PubMed  CAS  Google Scholar 

  10. 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.

    PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. Kuramoto, E., Yano, O., Kimura, Y., et al. (1992) Oligonucleotide sequences required for natural killer cell activation. Jpn. J. Cancer Res. 83, 1128–1131.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    PubMed  CAS  Google Scholar 

  14. 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.

    PubMed  CAS  Google Scholar 

  15. Wolff, J. A., Malone, R. W., Williams, P., et al. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468.

    Article  PubMed  CAS  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    PubMed  CAS  Google Scholar 

  24. 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.

    PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. 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.

    CAS  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. 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.

    Article  PubMed  CAS  Google Scholar 

  31. 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.

    Article  PubMed  CAS  Google Scholar 

  32. 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.

    Article  PubMed  CAS  Google Scholar 

  33. 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.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    PubMed  CAS  Google Scholar 

  35. 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.

    PubMed  CAS  Google Scholar 

  36. 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.

    Article  PubMed  CAS  Google Scholar 

  37. 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.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    PubMed  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. Hemmi, H., Takeuchi, O., Kawai, T., et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740–745.

    Article  PubMed  CAS  Google Scholar 

  43. 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.

    PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints 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

Publish with us

Policies and ethics