Current developments in viral DNA vaccines: shall they solve the unsolved?

This review describes the mechanisms of immune response following DNA vaccination. The efficacy of DNA vaccines in animal models is highlighted, especially in viral diseases against which no widely accepted vaccination is currently available. Emphasis is given to possible therapeutic vaccination in chronic infections due to persisting virus genomes, such as recurrent herpes (HSV-1 and HSV-2), pre-AIDS (HIV-1) and/or chronic hepatitis B (HBV). In these, the problem of introducing foreign viral DNA may not be of crucial importance, since the immunised subject is already a viral DNA (or provirus) carrier. The DNA-based immunisation strategies may overcome several problems of classical viral vaccines. Novel DNA vaccines could induce immunity against multiple viral epitopes including the conservative type common ones, which do not undergo antigenic drifts. Within the immunised host, they mimic the effect of live attenuated viral vaccines when continuously expressing the polypeptide in question. For this reason they directly stimulate the antigen-presenting cells, especially dendritic cells. The antigen encoded by plasmid elicits T helper cell activity (Th1 and Th2 type responses), primes the cytotoxic T cell memory and may induce a satisfactory humoral response. The efficacy of DNA vaccines can be improved by adding plasmids encoding immunomodulatory cytokines and/or their co-receptors.