Gene vaccination for the induction of immune tolerance

DNA vaccination is a strategy of immunization based on the injection of a gene encoding for a target protein with the goal of eliciting a potentially protective immune response in the host. Compared to traditional immunization procedures, DNA vaccination offers several advantages: increased availability of antigenic peptides because of the endogenous and long-term synthesis of the gene product, improved antigen processing and presentation, possibility of antigen structure modeling through molecular engineering, coexpression of immunologically relevant agents, and low cost of vaccine production. Although the choice of the most appropriate vector for gene transfer may still be controversial, the application of DNA vaccination to the treatment of autoimmune diseases in different experimental animal models has demonstrated the great potential of this procedure for therapeutic purposes. DNA vaccination has been successful in protecting mice from the development of organ-specific autoimmunity (experimental allergic encephalomyelitis (EAE), autoimmune diabetes, experimental arthritis, experimental uveitis) as well as systemic autoimmune disease (systemic lupus erythematosus (SLE), antiphospholipid syndrome). The protection appears to be highly influenced by the capacity of DNA vaccination to modulate immune responses affecting the Th1, Th2 and, importantly, the T cell immunoregulatory arms. We review here the experimental evidence and most recent data supporting the use of DNA vaccination in the induction of immune tolerance.