DNA vaccination to treat autoimmune diabetes

In numerous animal models, DNA immunization has been shown to induce protec tive immunity against infectious diseases (viral, bacterial and protozoan) and cancers (1, 2). In these situations it is desirable to induce a strong immune response to the DNA-encoded antigen in order to generate an immune m emory that enables the vaccine to respond more rapidly to subsequent challe nge. The success of DNA vaccination in this regard has led to its rapid int roduction into several human clinical trials (3, 4). However, in autoimmuni ty, undesirable immune responses to autoantigens are thought to lead to the destruction of target cells or organs, resulting in diseases such as myast henia gravis, diabetes or multiple sclerosis. Thus, at first sight, it appe ars that immunization would more likely trigger autoimmunity than ameliorat e it. Nevertheless, clinical experience has shown that certain immune-media ted diseases may be countered by low-dose antigen administration ('desensit ization'), although the underlying mechanisms remain somewhat conjectural. Here, we will describe an intriguing approach to the prevention of autoimmu ne disease, in which we use a DNA vaccine encoding a self-antigen to abroga te autoimmune diabetes. The success of this strategy relies on the nature o f the immune response induced by the DNA vaccine.