Autoimmunity, Allergy, and Genetic Vaccines

Abstract

Three parameters of the plasmid-based expression vectors may interfere with the homeostasis of the immune system, responsible for self—nonself discrimination and regulation of response to nonself. First, the presence of immune stimulatory unmethylated CpG motifs in bacterial DNA (Krieg, 1996; Tighe et al., 1998) is responsible for the Thl-promoting adjuvant activity. Second, the plasmid DNA itself acts like an antigen and may trigger the generation or enhancement of anti-DNA antibodies above pathological thresholds. Third, the antigens expressed by plasmid-based vectors may cross-react to a certain extent with self-antigens. These three properties, together with factors such as route, frequency, and dose of inoculation may be exploited, with the aim of preventing or suppressing autoimmune and allergic conditions. Furthermore, understanding the interplay among these factors will eventually allow for minimizing unwanted side effects of DNA-based vaccines.