Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine

OBJECTIVE: To assess the efficacy of intranasal administration of microgram amounts of type II collagen (CII) coupled to cholera toxin B subunit (CTB) with respect to the development of collagen-induced arthritis, even when given after the onset of clinically evident arthropathy. METHODS: DBA/1 mice were immunized with CII to induce arthritis and were subsequently treated with CTB-CII, CTB-conjugated ovalbumin, or CII alone. The incidence and severity of arthritis were assessed clinically and histologically. RESULTS: Treatment with CTB-CII conjugate effectively suppressed leukocyte infiltration into the synovium and prevented bone erosion. Comparable doses of unconjugated CII administered by the same route were relatively ineffective. Protection with nasal CTB-CII vaccine was associated with decreased production of interleukin-4 (IL-4), IL-6, and interferon-gamma and with reduced CII-specific IgG1 and IgG2a antibody responses in regional lymph nodes. CONCLUSION: Nasal treatment with CTB-CII appears to result in decreased peripheral Th1 and Th2 responses to collagen. These results suggest that intranasal vaccination with CTB-CII may offer an effective immunotherapeutic means for the control of chronic polyarthritis.