Urease is one of the key enzymes involved in the establishment of infection by the stomach-colonizing pathogen Helicobacter pylori. There combinant enzyme was co-administered intranasally 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. From the formulations tested, chitosan and alum-based adjuvants both elicited strong and sustained humor alurease-specific immunity, with the CTB þ MDP formulation shown to be superior. Following analysis of splenocyte proliferation, marked differences were seen in the concentrations of IL-2, IL-4, IL-6 and IFN-g in the supernatants of stimulated splenocytes, with profiles corresponding to antibody titre patterns. Compared to CTB, a strong inducer of all assayed cytokines, chitosan and alum adjuvants appeared to down-regulate IL-4induction, with no detectable IFN-g. In combination with CTB, MDP follows the same cytokine profile, albeit at rather lower levels, except forIL-2. We conclude that the CTB þ MDP combination offers significant potential with respect to urease-specific CD4þ cell induction, a process recently identified as essential for the clearance of H. pylori.
|Publication status||Published - Dec 2001|