PMID- 16135392 OWN - NLM STAT- MEDLINE DCOM- 20060227 LR - 20151119 IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 24 IP - 3 DP - 2006 Jan 16 TI - Interleukin-18 enhances Th1 immunity and tumor protection of a DNA vaccine. PG - 244-53 AB - 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. FAU - Marshall, Deborah J AU - Marshall DJ AD - Centocor, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. dmarsha1@cntus.jnj.com FAU - Rudnick, Kelly A AU - Rudnick KA FAU - McCarthy, Stephen G AU - McCarthy SG FAU - Mateo, Lani R San AU - Mateo LR FAU - Harris, Michael C AU - Harris MC FAU - McCauley, Christine AU - McCauley C FAU - Snyder, Linda A AU - Snyder LA LA - eng PT - Journal Article DEP - 20050815 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antimetabolites) RN - 0 (Cancer Vaccines) RN - 0 (Cytokines) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-18) RN - 0 (Vaccines, DNA) RN - G34N38R2N1 (Bromodeoxyuridine) SB - IM MH - Adjuvants, Immunologic MH - Animals MH - Antibody Specificity MH - Antimetabolites MH - Bromodeoxyuridine MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cancer Vaccines/*immunology MH - Cell Line, Tumor MH - Cell Proliferation MH - Cytokines/analysis/biosynthesis MH - Female MH - Immunoglobulin G/analysis/biosynthesis MH - Interleukin-18/*pharmacology MH - Kinetics MH - Mice MH - Mice, Inbred BALB C MH - Neoplasms/immunology/prevention & control MH - Plasmids/genetics MH - Stimulation, Chemical MH - T-Lymphocytes, Cytotoxic/immunology MH - Th1 Cells/*immunology MH - Vaccines, DNA/immunology EDAT- 2005/09/02 09:00 MHDA- 2006/02/28 09:00 CRDT- 2005/09/02 09:00 PHST- 2005/02/11 00:00 [received] PHST- 2005/07/29 00:00 [accepted] PHST- 2005/09/02 09:00 [pubmed] PHST- 2006/02/28 09:00 [medline] PHST- 2005/09/02 09:00 [entrez] AID - S0264-410X(05)00771-1 [pii] AID - 10.1016/j.vaccine.2005.07.087 [doi] PST - ppublish SO - Vaccine. 2006 Jan 16;24(3):244-53. doi: 10.1016/j.vaccine.2005.07.087. Epub 2005 Aug 15.