Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization

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

抄録

<jats:p>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-α, interferon-β, 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.</jats:p>

収録刊行物

  • Science

    Science 273 (5273), 352-354, 1996-07-19

    American Association for the Advancement of Science (AAAS)

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