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Int J Clin Exp Pathol 2013;6(3):326-333

Review Article
Daedalic DNA vaccination against self antigens as a treatment for chronic kidney disease

Yuan Min Wang, Jimmy Jianheng Zhou, Ya Wang, Debbie Watson, Geoff Yu Zhang, Min Hu, Huiling Wu, Guoping Zheng, Yiping Wang, Anne M
Durkan, David CH Harris, Stephen I Alexander

Centre for Kidney Research, Children’s Hospital at Westmead, Sydney, NSW, Australia; Centre for Transplant and Renal Research, University
of Sydney at Westmead Millennium Institute, Sydney, NSW Australia; Centre for Medical Bioscience, University of Wollongong, NSW Aus-tralia;
Collaborative Transplant Research Group, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia

Received December 10, 2012; Accepted January 17, 2013; Epub February 15, 2013; Published March 1, 2013

Abstract: Chronic kidney disease (CKD) is a major cause of death and morbidity in Australia and worldwide. DNA vaccination has been used
for targeting foreign antigens to induce immune responses and prevent autoimmune disease, viral infection and cancer. However, the use of
DNA vaccination has been restricted by a limited ability to induce strong immune responses, especially against self-antigens which are limited
by mechanisms of self-tolerance. Furthermore, there have been few studies on the potential of DNA vaccination in chronic inflammatory
diseases, including CKD. We have established strategies of DNA vaccination targeting specific self-antigens in the immune system including
co-stimulatory pathways, T cell receptors and chemokine molecules, which have been effective in protecting against the development of CKD in
a variety of animal models. In particular, we find that the efficacy of DNA vaccination is improved by dendritic cell (DC) targeting and can protect
against animal models of autoimmune nephritis mimicking human membranous nephropathy. In this review, we summarize several
approaches that have been tested to improve the efficacy of DNA vaccination in CKD models, including enhanced DNA vaccine delivery
methods, DNA vaccine modifications and new molecular targets for DNA vaccination. Finally, we discuss the specific application of DNA
vaccination for preventing and treating CKD. (IJCEP1212014).

Keywords: DNA vaccination, dendritic cell, DEC205, CD40, cytokine, costimulatory molecular, active Heymann nephritis (HN), adriamycin
nephropathy (AN)

Address correspondence to: Yuan Min Wang, Centre for Kidney Research, Children’s Hospital at Westmead, NSW 2145, Sydney, Australia.
Phone: (61-2) 98453106; Fax: 98453178; E-mail: yuan.wang@health.nsw.gov.au