Table 1 The safety concerns and possible solutions for plasmid DNA vaccines and their production hosts. A priori each safety concern should be addressed as early in development as possible.
| Â | Safety concern | Possible solution |
|---|---|---|
Genetic elements | Transfer of plasmid to host flora | Narrow host-range replication region Non-antibiotic plasmid marker |
| Â | Germline integration | Avoidance of mammalian replication region |
| Â | Insertional mutagenesis and oncogenesis | Artificial DNA for promoter, intron, and signal sequence Avoidance of human-homologous DNA |
| Â | Adverse effects of encoded peptide(s) | Artificial signal sequences Avoidance of mammalian replication region Evaluation of vaccine peptide case-by-case |
| Â | Induction of autoimmune reactions | Minimized plasmids |
Production host | Endotoxins and biogenic amines | Use of gram-positive organism |
| Â | Transferable antibiotic resistance genes | Determination of minimal inhibitory concentrations (MIC's) Screening for transferability |
| Â | Genetic instability | Analysis of plasmid population by sequencing and mass spectrometry |
| Â | Pathogenicity | Use of food-grade organism |