title: Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants.
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.
authors.affiliation: Dynavax Technologies Corporation, San Diego, California 92121, USA.
authors.forename: M
authors.initials: M
authors.lastname: Roman
authors.forename: E
authors.initials: E
authors.lastname: Martin-Orozco
authors.forename: J S
authors.initials: JS
authors.lastname: Goodman
authors.forename: M D
authors.initials: MD
authors.lastname: Nguyen
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Ronaghy
authors.forename: R S
authors.initials: RS
authors.lastname: Kornbluth
authors.forename: D D
authors.initials: DD
authors.lastname: Richman
authors.forename: D A
authors.initials: DA
authors.lastname: Carson
authors.forename: E
authors.initials: E
authors.lastname: Raz
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007372:Interferons / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics*; D008262:Macrophage Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*; D001616:beta-Galactosidase / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007378:Interleukins; D007073:Immunoglobulin E; D004247:DNA; D007372:Interferons; D001616:beta-Galactosidase