Currently available treatments for
rheumatoid arthritis (RA) are often ineffective in ameliorating the progression of disease, particularly the invasive destruction of articular cartilage and bone, and RA remains incurable. Therefore, vaccinotherapy of RA with an
antigen-specific tolerizing
DNA vaccine may offer new promise for overcoming this difficulty. Using recombinant technology, the DNA sequences encoding chicken
type II collagen (CCOL2A1) with deleted N-propeptides were obtained from the plasmid pPIC9K/pCalpha(1)(II), and then cloned into pcDNA3.1(+). The resulting recombinant plasmid pcDNA-CCOL2A1 was produced in Escherichia coli, purified, characterized and used as a tolerizing
DNA vaccine for the treatment of
collagen-induced arthritis (CIA). Therapeutic efficacy and potential action mechanisms of pcDNA-CCOL2A1 tolerizing
DNA vaccine against CIA were studied. Here we demonstrate that a single intravenous treatment with novel tolerizing
DNA vaccine pcDNA-CCOL2A1 can induce potent immune tolerance against CIA. The efficacy of this
therapy was verified by clinical visual scoring, radiographic X-ray, histopathological examination, and anti-CII
IgG levels. Furthermore, the action mechanism behind this efficacy can be at least partially attributed to increased CD4(+)CD25(+) T regulatory cells, which specifically down-modulate the T lymphocyte proliferative response to CCII, induce a shift of Th1 to Th2 cells, as well as down-regulate Th1-cytokine
TNF-alpha, while up-regulating both Th2-cytokine
IL-10 and Th3-cytokine
TGF-beta. More importantly, pcDNA-CCOL2A1 alone seems to be as effective as the current "golden standard" treatment,
methotrexate (MTX). Taken together, these results suggest that we have successfully developed a novel tolerizing
DNA vaccine encoding CCII, which is the first description of a tolerizing
DNA vaccine encoding CCII for
antigen-specific tolerizing
therapy but not prophylactic against CIA.