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.
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.
Dept of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3P4.
Qingdong
Q
Guan
Yanbing
Y
Ma
China-Li
CL
Hillman
Allan
A
Ma
Gang
G
Zhou
Gefei
G
Qing
Zhikang
Z
Peng
D000818:Animals; D000915:Antibody Affinity; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D003094:Collagen / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology / Q000628:therapy; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D014302:Trinitrobenzenesulfonic Acid; D014614:Vaccines, Synthetic / Q000276:immunology*
D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D014614:Vaccines, Synthetic; D014302:Trinitrobenzenesulfonic Acid; D003094:Collagen