Immunostimulatory DNA Sequences Function as T helper-1-promoting Adjuvants

Nat Med. 1997 Aug;3(8):849-54. doi: 10.1038/nm0897-849.

Abstract

An adjuvant role for certain short bacterial immunostimulatory DNA sequences (ISSs) has recently been proposed on the basis of their ability to stimulate T helper-1 (Th1) responses in gene-vaccinated animals. We report here that noncoding, ISS-enriched plasmid DNAs or ISS oligonucleotides (ISS-ODNs) potently stimulate immune responses to coadministered antigens. The ISS-DNAs suppress IgE synthesis, but promote IgG and interferon-gamma (IFN-gamma) production. They furthermore initiate the production of IFN-gamma, IFN-alpha, IFN-beta, and interleukins 12 and 18, all of which foster Th1 responses and enhance cell-mediated immunity. Consideration should be given to adding noncoding DNA adjuvants to inactivated or subunit viral vaccines that, by themselves, provide only partial protection from infection.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibody Formation / genetics
  • DNA / genetics
  • DNA / immunology*
  • Female
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Interferons / biosynthesis
  • Interleukins / biosynthesis
  • Lymphocyte Activation / genetics*
  • Macrophage Activation / genetics
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / immunology*
  • beta-Galactosidase / immunology

Substances

  • Adjuvants, Immunologic
  • Immunoglobulin G
  • Interleukins
  • Immunoglobulin E
  • DNA
  • Interferons
  • beta-Galactosidase