title: Interleukin-18 enhances Th1 immunity and tumor protection of a DNA vaccine.
abstract: DNA vaccines show efficacy in many preclinical models, but these results have not yet translated to consistent clinical efficacy. Co-administration of molecularly encoded adjuvants is one approach that may enable DNA vaccines to achieve enhanced immune response induction in humans. Interleukin-18 (IL-18) is a Th1-type cytokine that has been shown to augment the activity of DNA vaccines in some preclinical models. A prostate-specific antigen (PSA) DNA vaccine was tested in a mouse tumor model system to explore the impact of co-administration of a pIL-18 plasmid. Low doses of the pPSA vaccine were not capable of inducing tumor protection, but when pIL-18 was co-administered, complete tumor protection was observed in all mice. Tumor protection was mediated by both CD4(+) and CD8(+) T cells. Detailed analysis of the immune response in mice immunized with either pPSA or pPSA/pIL-18 demonstrated that pIL-18 skewed the PSA-specific immune response toward Th1. More importantly, stronger CD4(+) and CD8(+) T cell responses developed in the pPSA/pIL-18-immunized mice, with faster kinetics. These results suggest that IL-18 is a powerful adjuvant molecule that can enhance the development of antigen-specific immunity and vaccine efficacy.
authors.affiliation: Centocor, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. dmarsha1@cntus.jnj.com
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Marshall
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Rudnick
authors.forename: Stephen G
authors.initials: SG
authors.lastname: McCarthy
authors.forename: Lani R San
authors.initials: LR
authors.lastname: Mateo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Harris
authors.forename: Christine
authors.initials: C
authors.lastname: McCauley
authors.forename: Linda A
authors.initials: LA
authors.lastname: Snyder
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000918:Antibody Specificity; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D020382:Interleukin-18 / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control; D010957:Plasmids / Q000235:genetics; D013268:Stimulation, Chemical; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000963:Antimetabolites; D019496:Cancer Vaccines; D016207:Cytokines; D007074:Immunoglobulin G; D020382:Interleukin-18; D019444:Vaccines, DNA; D001973:Bromodeoxyuridine