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

Abstract
Mucosal administration of autoantigen HSP65 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 cytokines IL-10 and IL-4 secretion, and reduced proliferation in nasal administration of the fusion protein HSP65-6xP277. 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.
AuthorsJin Liang, Zhu Aihua, Wang Yu, Lu Yong, Liu Jingjing
JournalVaccine (Vaccine) Vol. 28 Issue 19 Pg. 3312-7 (Apr 26 2010) ISSN: 1873-2518 [Electronic] Netherlands
PMID20226247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Autoantigens
  • Drug Carriers
  • Heat-Shock Proteins
  • heat-shock protein 65, human
Topics
  • Administration, Intranasal
  • Animals
  • Autoantigens (administration & dosage, immunology)
  • Diabetes Mellitus, Type 1 (immunology, prevention & control)
  • Drug Carriers (administration & dosage)
  • Female
  • Heat-Shock Proteins (administration & dosage, immunology)
  • Humans
  • Inflammation (immunology, prevention & control)
  • Mice
  • Mice, Inbred NOD

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