Controlled Plasmid Delivery and Gene Expression: Applications for Nucleic Acid-Based Vaccines

Abstract

After the concept of genetic immunization was first demonstrated by Johnston's group in 1992 (1), numerous studies have reported the potential prophylactic and therapeutic use of nucleic acid-based vaccines for combating various infectious diseases (2-4). Vaccines of this composition appear to be both efficacious in the short term, and able to elicit a prolonged anamnestic response capable of preventing or resolving infection when challenged at up to one year after vaccination (5). Nucleic acid-based vaccines elicit a broader immune response than do subunit vaccines, inducing both cellular and humoral responses that are reminiscent of attenuated and whole-killed viral vaccines. Further, nucleic acid-based vaccines can be prepared with relative ease of synthesis and production. Expression plasmids can be generated quickly once the antigen's coding sequence is known and small- and large-scale purification methods are well established. Nucleic acid-based vaccines also avoid some of the safety concerns of conventional vaccines in that there is no chance of disease due to co-purification of contaminating virus or reversion of the attenuated strain in the patient. This is not to claim that the safety issues surrounding nucleic acid-based vaccines are minimal. The major theoretical concerns surrounding the safety of this technology include plasmid integration into the host genome, transformation of somatic or stem cells, and tolerability. However, there is no published evidence that administration of unformulated or 'naked' plasmid produces a severe short or long term deleterious effect (6).