Urease is one of the key enzymes involved in the establishment of infection by the stomach-colonizing pathogen Helicobacter pylori.The recombinant enzyme was co-administered parenterally with a range of adjuvants and their combinations. Over 6 months, we measured a number of immunological parameters to characterize both the intensity and quality of the ensuing immune responses. Of the formulations test-ed, alum þ Quil-A gave the highest peak humoral antibody titres, with chitosan and alum þ MDP reaching comparable levels. In contrast, MDP induced a lower response, however, titres were sustained throughout the duration of the study. Following splenocyte proliferation and supernatant cytokine analysis, alum þ MDP showed by far the highest proliferation index, with corresponding increased IL-2, IL-4, IL-6 and IFN-g concentrations. Alum þ Quil-A, produced the second highest proliferation index,superseding the alum þ MDP formulation only in IL-2 levels. Otherwise,IFN-g was observed only in the chitosan and alum formulations, chitosan being the only up-regulator of IL-4 alone or in combination with MDP,apart from free rURE. Surprisingly, MDP alone showed very low proliferation, with very low IL-6 and strongly down-regulated IL-4. In conclusion, the alum adjuvant combinations with MDP or Quil-A offer a significant potential in the process of eliciting CD4þ cells recently identified as essential for H. pylori clearance.
|Published - Dec 2001