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 g iven after the onset of clinically evident arthropathy, Methods. DBA/1 mice were immunized with CII to induce arthritis and were su bsequently treated with CTB-CII, CTB-conjugated ovalbumin, or CII alone. Th e incidence and severity of arthritis were assessed clinically and histolog ically. 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 ineffec tive. Protection with nasal CTB-CII vaccine was associated with decreased p roduction of interleukin-4 (IL-4), IL-6, and interferon-gamma and with redu ced CII-specific IgG1 and IgG2a antibody responses in regional lymph nodes. Conclusion. Nasal treatment with CTB-CII appears to result in decreased per ipheral Th1 and Th2 responses to collagen. These results suggest that intra nasal vaccination with CTB-CII may offer an effective immunotherapeutic mea ns for the control of chronic polyarthritis.