4.5 Article

Development of recombinant vaccines against IL-12/IL-23 p40 and in vivo evaluation of their effects in the downregulation of intestinal inflammation in murine colitis

期刊

VACCINE
卷 27, 期 50, 页码 7096-7104

出版社

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.09.058

关键词

IL-12; IL-23; Vaccine; Crohn's disease; Immunotherapy

资金

  1. Canadian Institutes of Health Research [MOP 68959]
  2. Crohn's & Colitis Foundation of Canada
  3. Manitoba Institute of Child Health, Inc

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Overexpression of IL-12 and IL-23, which share the p40 subunit, has been implicated in the pathogenesis of Crohn's disease. Targeting these cytokines with monoclonal antibodies has emerged as a new and effective therapy, but one with adverse reactions. In this study. we sought to develop p40 peptide-based virus-like particle vaccines that elicit autoantibodies to IL-12 and IL-23 for a long-term treatment of the disease. Three vaccines (named C, D and F) against the p40 were developed by inserting peptides derived from p40 into the carrier, hepatitis B core antigen, using molecular engineering methods. Immunization with the vaccines, without the use of adjuvants, induced high titered and long-lasting antibodies to IL-12, IL-23 and p40. The three vaccines were evaluated in vivo in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced chronic murine colitis. Mice were immunized with a vaccine three times, followed by weekly intrarectal administrations of TNBS. Vaccine groups, especially groups C and F, showed reduced expression of IL-12/IL-23p40, less inflammation, and decreased collagen deposition in colon tissues when compared with controls. We concluded that IL-12/IL-23p40 vaccines may be a potential therapeutic approach in the treatment of Crohn's disease and other autoimmune diseases. (C) 2009 Elsevier Ltd. All rights reserved.

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