Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization

作者：Yukio Sato, Mark Roman, Helen Tighe, Delphine J. Lee, Maripat Corr, Minh‐Duc Nguyen, Gregg J. Silverman, Martin Lotz, Dennis Anthony Carson, Eyal Raz · 发表于：Science · 年份：1996 · DOI：10.1126/science.273.5273.352 · 被引用次数：1065 · 研究领域：RNA Interference and Gene Delivery、Immunotherapy and Immune Responses、Viral gastroenteritis research and epidemiology

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.