Abstract

The goal of immunoregulatory DNA vaccination is the antigen- and tissue-specific suppression of pathological inflammation that underlies immune-mediated inflammatory disorders like autoimmune diseases and allograft rejection. Recent patents and patent applications have applied immunoregulatory DNA vaccines in rodent model systems and human clinical trials using plasmid DNA coding for autoantigens such as insulin and glutamic acid decarboxylase for type 1 diabetes, myelin-associated proteins for multiple sclerosis, and heat sock protein 60 for rheumatoid arthritis. In these cases, the objective is to induce a homeostatic-like regulatory immune response to suppress pathological inflammation. In addition, patent applications have disclosed the use of DNA vaccines encoding the pro-inflammatory MIF cytokine and the CD25 IL-2 receptor subunit to interfere with the inflammatory process. Approaches have also been taken to improve DNA vaccination efficacy, including covalent modification of plasmid DNA, engineering secretion of vaccine-encoded antigen, and co-delivery of DNA coding for anti-inflammatory cytokines, a mutant co-stimulatory molecule, a growth factor, or a pro-apoptotic protein. Furthermore, a patent application has disclosed the use of a DNA vaccine previously shown to treat successfully an autoimmune disease to prolong allograft survival. Taken together, these patents and patent applications indicate a promising bench-to-bedside potential for immunoregulatory DNA vaccination applied to autoimmune diseases and allograft rejection.

Keywords: Autoimmune disease, clinical trial, CpG dinucleotide, DNA vaccine, immune tolerance, inflammation, molecular adjuvant, organ transplantation, rodent model system, Immunoregulatory DNA Vaccines, Allograft Rejection, prophylactic, viral vaccines, somatic cells, modulate immune responses, multiple clinical, multiple sclerosis (MS), type 1 diabetes (T1D), antigen-presenting cells (APCs), immune-mediated inflammatory disorders (IMIDs), systemic immunosuppressants, dendritic cell, cytokines, chemokines, pathogenic inflammation, ameliorate disease, vaccine-encoded antigen, rheumatoid arthritis (RA), Multiple sclerosis, T cell-media-ted disease, myelin basic protein (MBP), T lymphocytes, B lymphocytes, autoantibodies, insulin B-chain, Secreted GAD, US7381711 (2008), US7544669 (2009), US20080194510, Pancreatic antigen, Cohen and Quintana, lymph nodes (LNs), LCNM NP-specific cytotoxic T cells, IL-10, IL-4, GAD65, non-obese diabetic (NOD), anti-GAD IgG1, anti-apoptotic activity, Th2 cytokine, co-stimulatory anti-CD28 antibodies, PLP139-151, PLP139-151 DNA, polynucleotide therapy, sGAD + BAX, anti-inflammatory Il-10, Tgf-b genes, Foxp3 gene, co-stimulatory molecules, tolerogenic DNA vaccines