Abstract
Abstract: :
Purpose: We have been exploring DNA vaccination to retinal autoantigen, IRBP, as preventive therapy against EAU, a Th1 mediated disease, which serves as a model of human uveitis. Methods: Mice vaccinated hydrodynamically with 10 µg IRBP–DNA were protected from EAU development induced by a subsequent uveitogenic challenge with IRBP protein in adjuvant for at least 10 weeks. Results: Mice vaccinated with 80 µg DNA, although similarly protected from active induction of EAU, developed a low grade, transient ocular inflammation from vaccination alone. Antigen–specific responses of vaccinated, but unchallenged, mice 6 weeks after vaccination showed a measurable IFN–γ response to IRBP in the high–dose, but not in the low–dose vaccinated animals. Antigen–specific IFN–γ production after EAU challenge was reduced in animals protected either by high or by low dose vaccination. Conclusion: These data suggest that while DNA vaccination can be protective from actively induced EAU, it may carry an element of risk. Careful optimization of treatment dose can help to retain the protective effect of the vaccine, while minimizing the risk of side effects.
Keywords: autoimmune disease • immunomodulation/immunoregulation • uveitis–clinical/animal model