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

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Abstract
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‐γ 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.

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