Immunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization

TLDR

Vaccination with naked DNA elicits cellular and humoral immune responses biased toward T helper type 1 cells, yet plasmid vectors expressing large amounts of gene product do not necessarily induce immune responses to the encoded antigens. The immunogenicity of plasmid DNA requires short immunostimulatory DNA sequences (ISS) that contain a CpG dinucleotide in a specific base context. Human monocytes transfected with pDNA or double‑stranded oligonucleotides containing ISS, but not ISS‑deficient ones, produced large amounts of interferon‑α, interferon‑β, and interleukin‑12, demonstrating that ISS are required for gene vaccination yet simultaneously down‑regulate gene expression and may hinder gene replacement therapy by inducing proinflammatory cytokines.

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.