Original research

DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes

Rubens R Santos Junior^1,2 , Alexandrina Sartori³ , Deison S Lima¹ , Patrícia RM Souza¹ , Arlete AM Coelho-Castelo¹ , Vânia LD Bonato¹ and Célio L Silva¹

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

author email corresponding author email

Journal of Immune Based Therapies and Vaccines 2009, 7:4doi:10.1186/1476-8518-7-4

Published:	15 September 2009

Abstract

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.