The opposing effects of lipopolysaccharide on the antitumor therapeutic efficacy of DNA vaccine.
DNA vaccine represents a novel method to elicit immunity against infectious disease. Lipopolysaccharide (LPS) copurified with plasmid DNA may affect therapeutic efficacy and immunological response. We aimed to study the effect of LPS on the therapeutic efficacy of HER-2/neu DNA vaccine in a mouse tumor animal model. Plasmid DNA purified from commercial EndoFree plasmid purification kits functioned as a better therapeutic DNA vaccine than that purified from Non-EndoFree purification kit, which contains >or=0.5 microg LPS per 100 mg DNA plasmid. To further investigate the effect of LPS on the therapeutic efficacy of DNA vaccine, increasing amount of LPS was added to endotoxin-free plasmid DNA, and inoculated on mice with established tumors. One mug of LPS significantly attenuated the therapeutic effect of neu DNA vaccine and increased Th2 immune responses bias with interleukin-4 cytokine production. In contrast, high amount (100 microg) of LPS enhanced the therapeutic efficacy of neu DNA vaccine with an increase of cytotoxic T lymphocyte response and Th1 immune response. The effect of LPS on DNA vaccine was diminished when the tumor was grown in toll-like receptor 4 (TLR4)-mutant C3H/HeJ mice. Our results indicate that variation in the LPS doses exerts opposing effects on the therapeutic efficacy of DNA vaccine, and the observed effect is TLR4 dependent.
Lin
Chi-Chen
CC
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Yang
Huei-Jiun
HJ
Tu
Cheng-Fen
CF
Lai
Ming-Derg
MD
D000818:Animals; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018734:Genes, erbB-2 / Q000276:immunology; D015316:Genetic Therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*; D019444:Vaccines, DNA / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis
D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019444:Vaccines, DNA