Cimetidine enhances the protective effect of GST DNA vaccine against Schistosoma japonicum

Cimetidine (CIM), a histamine-2-receptor antagonist, has a long history of safe use in gastric acid-mediated gastrointestinal disorders. In this study, we used CIM, as an adjuvant, with pEGFP-Sj26 GST (the recombinant plasmid containing enhanced green fluorescent protein gene and the gene encoding 26 kDa glutathione S-transferase of Schistosoma japonicum) DNA vaccine to immunized mice and attempted to enhance the protective effect against S. japonicum. The results showed that the reduction rate of worm and egg burdens in the pEGFP-Sj26GST plus CIM group were 79.0% and 68.4%, respectively, significantly higher than that in pEGFP-Sj26GST alone group (27.0% and 22.5%, P < 0.01). Compared with the pEGFP-Sj26GST alone group, mice immunized with pEGFP-Sj26GST plus CIM showed an elevated level of IFN-γ and IL-12 and a low level of IL-10 in splenocytes, while the levels of IL-4 and IL-5 showed no difference between the two groups. Our data also demonstrated that the percentage of CD4+CD25+ regulatory T cells (Tregs) was significantly decreased in the spleens of mice immunized with pEGFP-Sj26GST plus CIM. All these findings suggest that CIM as a potential schistosome DNA vaccine adjuvant can enhance the protective effect of pEGFP-Sj26GST vaccine.

In this paper we used cimetidine (CIM) with pEGFP-Sj26GST DNA vaccine to immunize mice. The results showed that CIM greatly enhanced the protective effect of the vaccine against Schistosoma japonicum. Moreover, this study has also revealed that vaccination of mice with pEGFP-Sj26GST DNA vaccine plus CIM can significantly down-regulate the CD4+CD25+ regulatory T-cells ..Highlights► Cimetidine (CIM) can greatly enhance the protection of pEGFP-Sj26GST DNA vaccine against Schistosoma japonicum. ► CIM can significantly down-regulate the CD4+CD25+ Tregs and augment Th1 response. ► The mechanism of CIM improving protection of vaccine may be involved in enhancing Th1 response and reducing CD4+CD25+ Tregs.