有效皮内基因免疫所需的免疫刺激DNA序列。

Immunostimulatory DNA sequences necessary for effective intradermal gene immunization.

作者信息

Sato Y, Roman M, Tighe H, Lee D, Corr M, Nguyen M D, Silverman G J, Lotz M, Carson D A, Raz E

机构信息

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.

出版信息

Science. 1996 Jul 19;273(5273):352-4. doi: 10.1126/science.273.5273.352.

DOI:10.1126/science.273.5273.352

PMID:8662521

Abstract

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.

摘要

裸DNA疫苗接种可引发具有1型辅助性T细胞偏向性的细胞免疫和体液免疫反应。然而，表达大量基因产物的质粒载体不一定能诱导针对编码抗原的免疫反应。相反，质粒DNA（pDNA）的免疫原性需要短的免疫刺激DNA序列（ISS），这些序列在特定碱基背景下含有CpG二核苷酸。用pDNA或含有ISS的双链寡核苷酸转染的人单核细胞，而不是用缺乏ISS的pDNA或寡核苷酸转染的单核细胞，会转录大量的α干扰素、β干扰素和白细胞介素-12。虽然ISS对于基因疫苗接种是必需的，但它们会下调基因表达，因此可能通过诱导促炎细胞因子来干扰基因替代疗法。