HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 inducing anti-inflammatory immune response in NOD mice by nasal administration

Mucosal administration of autoantigen 1451,65 can induce anti-inflammatory immune response and decrease organ-specific inflammation and disease in several models of autoimmunity, such as arthritis and atherosclerosis We have been interested in whether the HSP65 serves as an immunogenic carrier for a diabetogenic peptide P277 can also Induce anti-inflammatory immune response in NOD mice by mucosal administration Thus, the dual functions of anti-type 1 diabetes of HSP65 and P277 will be obtained To test this hypothesis, we examined the effect of intranasal vaccination with P277 tandem repeat sequences carried by HSP65 in the absence of adjuvants on autoimmune diabetes in NOD mice. We found a significant decrease in the incidence of diabetes, inhibition of insulitis, reduction in IgG2a isotype antibodies to P277 and proinflammatory cytokines IFN-gamma and IL-2 secretion, increased IgG1, IgG2b subclass antibodies to P277 and anti-inflammatory cytokmes IL-10 and IL-4 secretion, and reduced proliferation in nasal administration of the fusion protein HSP65-6 x P277 Our results demonstrate that HSP65 may serve as a particularly advantageous carrier for P277-based vaccines and mucosal administration may be a therapeutic approach for treatment of type 1 diabetes. (C) 2010 Elsevier Ltd. All rights reserved