title: A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis.
abstract: OBJECTIVE
  Previous studies have demonstrated that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibodies decreases joint inflammation and destruction in a type II collagen-induced arthritis model in mice. The aim of this study was to develop and describe a simple and effective method of active immunization that induces anti-MIF autoantibodies, which may neutralize MIF bioactivity.
  
  
  METHODS
  We developed a MIF DNA vaccine by introducing oligonucleotides encoding a tetanus toxoid (TTX) Th cell epitope into the complementary DNA sequence of murine MIF. Mice were injected with this construct in conjunction with electroporation. The ability of this immunization to inhibit the development of collagen antibody-induced arthritis (CAIA) in BALB/c mice and spontaneous autoimmune arthritis in interleukin-1 receptor antagonist (IL-1Ra)-deficient mice was then evaluated.
  
  
  RESULTS
  Mice that received the MIF/TTX DNA vaccine developed high titers of autoantibodies that reacted to native MIF. Compared with unvaccinated mice, vaccinated mice also produced less serum tumor necrosis factor alpha after receiving an intravenous injection of lipopolysaccharide. In addition, vaccination with MIF/TTX DNA resulted in significant amelioration of both CAIA in BALB/c mice and symptoms of autoimmune arthritis in IL-1Ra-knockout mice.
  
  
  CONCLUSIONS
  These results suggest that MIF/TTX DNA vaccination may be useful for ameliorating the symptoms of rheumatoid arthritis.
authors.affiliation: Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Onodera
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohshima
authors.forename: Harukazu
authors.initials: H
authors.lastname: Tohyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yasuda
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Ikkei
authors.initials: I
authors.lastname: Matsuda
authors.forename: Akio
authors.initials: A
authors.lastname: Minami
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Koyama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D003094:Collagen; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007596:Joints / Q000473:pathology / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D013745:Tetanus Toxoid / Q000032:analysis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019444:Vaccines, DNA / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D001323:Autoantibodies; D053590:Interleukin 1 Receptor Antagonist Protein; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D003094:Collagen; D004247:DNA; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse