Table 4.

Potential concerns regarding DNA vaccination

Theoretical issues	Concern	Resolution
Integration	DNA vaccines integrate into cellular DNA owing to optimized expression plasmids, resulting in insertional mutagenesis, chromosomal instability, or activation or inactivation of tumour suppressor genes	US Food and Drug Administration requires integration studies for new DNA products using accepted assays in animals before beginning human trials
Autoimmunity	Development of autoimmune disorders against patient DNA	Studies have shown this result is unlikely: no anti-nuclear or disease associated anti-DNA antibodies have been detected
	Development of autoantibodies against immune adjuvants	Examine patients for signs of autoimmunity using laboratory markers
Antibiotic resistance	Production process involves selection of bacterial cells using antibiotic resistance, which is conferred by a plasmid gene.	Antibiotic resistance in plasmid is driven by bacterial origin of replication (not mammalian)
	There is a risk that antibiotic resistance is transferred to patients receiving vaccine through the unintentional transfer of bacteria	Antibiotics used are restricted to antibiotics not commonly used to treat human infections
Low immunogenicity	First-generation DNA plasmids elicit low levels of T cell and B cell memory	Use novel formulations, immune plasmid adjuvants and delivery systems to enhance immunogenicity. Prime-boost approaches are common in clinical studies