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Content archived on 2024-06-25

Development of a novel DNA vaccine and identification of an autoantigen relevant to type I diabetes

Objective

Insulin-dependent diabetes mellitus (IDDM, type I diabetes) is a metabolic autoimmune disease in humans in which the ß cells of the islets of Langerhans are selectively destroyed. To date, no cure has been developed for this disease. While it has been established that the destruction of this tissue predominantly occurs due to auto-reactive recognition by CD4 T cells, the etiology of this disease as well as many of the autoantigens recognized by these T cells, are unknown.

Certain major histocompatibility com plex (MHC) class II alleles have been strongly linked with IDDM, such as DQ8 in humans and I-Ag7 in the non-obese diabetic (NOD) mouse, a spontaneous model for type I diabetes. In order to find a cure for IDDM, the target antigens that drive auto-reactive T cell recognition need to be identified and new immunotherapies need to be developed. Therefore, the main objectives of this project are the identification of one of these auto-antigens as well as the development of a novel DNA vaccine. To reach the first objective, several new in silico and in vitro approaches will be used for the identification of antigen candidates, that could possibly be recognized by a well characterized diabetogenic T cell clone called BDC2.5. Recombinant antigens will be generated in order to screen for the activation of BDC2.5.

We will finally evaluate the natural T and B cell response against this autoantigen in vivo in the NOD mouse in order to assess the value of protein homologues for the development of new diagnostics for disease prediction in humans. The second objective will be the generation of a novel DNA vaccine coding for soluble I-Ag7/peptide dimers. We will use the BDC2.5 system as a model to explore its efficacy in the NOD mouse. I-Ag7/peptide tetramers will allow us to evaluate the specific T cell response quantitatively as well as qualitatively. These experiments will facilitate the design of equivalent vaccines for the prevention of IDDM in human patients.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2002-MOBILITY-12
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Funding Scheme

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IRG - Marie Curie actions-International re-integration grants

Coordinator

UNIVERSIDAD DE BARCELONA
EU contribution
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Address
Gran Via de les Corts Catalanes, 585 (Vicerectorat de Recerca; OPER)
BARCELONA
Spain

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Total cost

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