RT Journal Article
SR Electronic
T1 Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization
JF Science
JO Science
FD American Association for the Advancement of Science
SP 352
OP 354
DO 10.1126/science.273.5273.352
VO 273
IS 5273
A1 Sato, Yukio
A1 Roman, Mark
A1 Tighe, Helen
A1 Lee, Delphine
A1 Corr, Maripat
A1 Nguyen, Minh-Duc
A1 Silverman, Gregg J.
A1 Lotz, Martin
A1 Carson, Dennis A.
A1 Raz, Eyal
YR 1996
UL http://science.sciencemag.org/content/273/5273/352.abstract
AB 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.