DNA vaccines: safety and efficacy issues

Abstract

DNA technology has been harnessed to produce a variety of plasmid-based vaccines designed to prevent viral, bacterial and parasitic infections. The rapid adoption and implementation of this novel vaccine strategy carries with it important safety and efficacy concerns. This review will focus on whether DNA vaccines (1) are likely to induce systemic or organ-specific autoimmune disease, (2) have the potential to induce tolerance rather than immunity, and (3) are as effective in individuals with depressed immune function as they are in healthy adults.

Spontaneous cellular uptake of exogenous messenger RNA in vivo is nucleic acid-specific, saturable and ion dependent

“…4 But, the direct injection of naked mRNA for vaccination or gene complementation remained quite unexplored, being reported in only four articles from three different teams [5][6][7][8] (for a review on mRNA-based vaccines, see Pascolo 9 ). Because of the safety (minimal vector, completely and naturally catabolized in several hours), ease (no need for infrastructures for cell culture) and versatility (any mRNA of interest can be produced) of naked mRNA-based therapies compared to DNAbased therapies, 10,11 we decided to study and improve the intradermal delivery of this genetic vehicle. As shown in Figure 1, using intradermal injection of globin UTR-stabilized (RNActive, CureVac GmbH, Tü bingen, Germany) luciferase-encoding mRNA in the ear pinna, 12 we could investigate the effect of the injection solution composition on the efficacy of in vivo mRNA transfer (for method details, see Supplementary Information and Supplementary Figure S1).…”

Feline Leukemia Virus DNA Vaccine Efficacy Is Enhanced by Coadministration with Interleukin-12 (IL-12) and IL-18 Expression Vectors

“…Alternatively, anti-DNA or anti-cytokine antibodies, produced as a result of immunization with plasmid DNA or in vivo expression of cytokine adjuvant DNA constructs (48,71), may have interfered with the humoral immune response against the antigenic components of the DNA vaccine (36). If such inhibition did occur, it was not a permanent effect, since after challenge high levels of virus-neutralizing antibodies appeared in all but two of the cats that did not develop a persistent infection.…”

Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation

“…Telomerase knockout mice (at generation 4) were produced by Dr. C. Greider (The Johns Hopkins University, Baltimore, MD) and provided by Dr. K. Hathcock (National Cancer Institute, National Institutes of Health, Bethesda, MD). All DNA obtained was repurified to eliminate endotoxin (Ͻ0.1 U/mg) (28) and was made single stranded by heat denaturation at 95°C for 5 min, followed by cooling on ice. BAL-31 (New England Biolabs, Beverly, MA) digestion of CT DNA was performed at 30°C for 90 min as recommended by the manufacturer.…”