DNA vaccines: safety aspect assessment and regulation.

For licensing purposes, besides the immunogenic aspects, deoxyribonucleic acid (DNA) vaccines present safety considerations that must be critically assessed during preclinical or/and clinical safety studies. The major concerns with regard to safety are integration of the plasmid DNA into the host genome, adverse immunopathological effects, the formation of anti-DNA antibodies resulting in auto-immune disease and the use of novel molecular adjuvants. Moreover, for veterinary vaccines intended to be used in husbandry animals, food safety aspects will become an important issue. All new vaccine candidates should therefore be thoroughly tested in target animals, keeping in mind that for food producing animals, the products will be consumed. Finally, a further safety aspect of interest concerns the possible spread of genetic material to the environment, by the potential transformation of the environmental microflora with only a few copies of complete or fragmented plasmid. These are issues that need to be considered in the final scientific decisions underpinning the registration of vaccines. Thus, to establish criteria for guidance and regulations for industry and licensing authorities, a project has been initiated to assess such risks of plasmid DNA vaccinations. Major emphasis will be placed on aspects such as the biodistribution of plasmid in vaccinated animals. This paper is intended as a contribution to the debate on the use of biotechnology in the future and should facilitate further discussions on the various safety aspects of DNA-based immunisations.