Original research
DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes
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* Corresponding author: Célio L Silva clsilva@fmrp.usp.br
1 University of São Paulo, Ribeirão Preto Medical School, Department of Biochemistry and Immunology, Ribeirão Preto, São Paulo, Brazil
2 Department of Clinical Analyses, School of Pharmaceutical Sciences, São Paulo State University, Araraquara, São Paulo, Brazil
3 Bioscience Institute, São Paulo State University, Botucatu, São Paulo, Brazil
Journal of Immune Based Therapies and Vaccines 2009, 7:4 doi:10.1186/1476-8518-7-4
Published: 15 September 2009Abstract
Background
Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.
Methods
In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.
Results
DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.
Conclusion
The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.