Sustained suppression of IL-18 by employing a vaccine ameliorates intestinal inflammation in TNBS-induced murine colitis

Aim: To develop IL-18 peptide-based virus-like particle vaccines that elicit autoantibodies against IL-18 and to evaluate the in vivo effects of the vaccines in murine colitis. Methods: Recombinant IL-18 vaccines were constructed, and the effects of the vaccines were evaluated in trinitrobenzene sulfonic acid-induced acute and chronic colitis in mice. Results: Two murine IL-18 peptide-based vaccines (A and D) were developed, which induced relative long-lasting specific antibodies against IL-18. Vaccine-immunized mouse antisera could partially block IL-18-induced IFN-gamma production in vitro. Mice receiving vaccine D, not vaccine A, had a significant decrease in intestinal inflammation, collagen deposition and pro-inflammatory cytokine levels in colon tissue. Conclusion: IL-18 vaccine may provide a potential therapeutic approach in the treatment of Crohn's disease. Lay abstract: Many proinflammatory cytokines, including IL-18, play important roles in exaggerating the disease progression of inflammatory bowel disease (IBD). Inflammatory bowel disease is a chronic autoimmune disease, which usually requires long-term treatment. Blocking these proinflammatory cytokines by using monoclonal antibodies has shown certain clinical efficacy, but it requires repeated injection of these antibodies. To induce relative long-lasting antibodies, we developed IL-18 peptide-based virus-like particle vaccines and evaluated their therapeutic effects in a murine colitis model. Our results showed that immunization of mouse with IL-18 peptide-based vaccine could improve murine colitis, which indicated this vaccine strategy might be a potential treatment approach.