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

Exp Parasitol. 2011 Aug;128(4):427-32. doi: 10.1016/j.exppara.2011.05.012. Epub 2011 May 23.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibodies, Helminth / blood
  • Cell Proliferation
  • Cimetidine / pharmacology*
  • Cytokines / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glutathione Transferase / genetics
  • Glutathione Transferase / immunology
  • Histamine H2 Antagonists / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Random Allocation
  • Schistosoma japonicum / drug effects
  • Schistosoma japonicum / genetics
  • Schistosoma japonicum / immunology*
  • Schistosomiasis japonica / prevention & control*
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Vaccines, DNA* / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Helminth
  • Cytokines
  • Histamine H2 Antagonists
  • Vaccines, DNA
  • Cimetidine
  • Glutathione Transferase