Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection

In vivo delivery of DNA encoding antigens is a simple tool to induce immune responses against pathogens. This approach to vaccination also offers the possibility to codeliver plasmids encoding immunomodulatory molecules in or der to drive immune responses towards optimal protective effects. In the mu rine model of Schistosoma mansoni infection, vaccination inducing a Th1 pro file has been shown to be protective. In this study, we used a plasmid enco ding the Th1-promoting cytokine IL-18, since we observed that percutaneous infection of Balb/c mice strongly induced the production of IL-18 mRNA in t he skin. Intradermal injection of the IL-18-encoding plasmid prior to infec tion did not interfere with parasite migration through the skin although it led to a local and transient cellular infiltration. When the IL-18-encodin g plasmid was codelivered with a S. mansoni glutathione S-transferase (Sm28 GST)-encoding plasmid, a 30-fold increase of antigen-specific IFN-gamma sec retion by spleen cells was observed in comparison to spleen cells from mice that had received only the Sm28GST-encoding plasmid. This immunostimulator y effect was related to a significant protective effect (28% reduction in e gg laying and 23% reduction in worm burden) which was attributed to a coope rative effect between both plasmids. Therefore, this study shows that codel ivery of an IL-18-encoding plasmid with an antigen-encoding plasmid can sti mulate specific cellular responses and induce protective effects against S. mansoni infection. (C) 2001 Elsevier Science Ltd. All rights reserved.