Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Inflammatory bowel disease is considered as an autoimmune disease, induced by over-production of some immune mediators. Currently, monoclonal antibodies against these mediators have been used to neutralise the mediators for the treatment of the disease. This therapy has been successful clinically. However, the monoclonal antibodies act as passively administered antagonists with short half-lives. Repeated injections are required to maintain the effects. Side effects include acute infusion reactions and the development of antibodies to the infused monoclonal antibodies which occurs in 60 % of the patients receiving the treatment. Another highly relevant concern is the extremely high cost (> $20,000/year/patient) associated with such passively administered therapeutics. These disadvantages limit the usefulness of this approach, as inflammatory bowel disease is chronic and requires long-term treatment. To overcome these disadvantages, we propose to develop an active immunotherapy using vaccines against these over-produced mediators for the treatment of inflammatory bowel disease, for example interleukin-12 and interleukin-23. We will develop recombinant vaccines against these cytokines and test the effect of the vaccines in a murine model of colitis. Administration of the vaccine will induce auto-antibodies to neutralise the over-expressed mediators, and therefore improve colitis symptoms in mice. This strategy will provide a long-lasting impact in the treatment of inflammatory bowel disease and, by extension, other diseases where over-expressed mediators play a pivotal role in pathogenesis. In addition, this active immunization strategy may also serve as a new research tool that provides a persistent inhibition of the target. This has been difficult to achieve with the knockout or transgenic methods currently used.