Maximilian Gabler

Dna Replicons: Next-generation Vaccines Against Allergy Maximilian Gabler

In this study, DNA vaccines based on alphaviral replicases (DNA replicons) were evaluated with respect to their protective and therapeutic capacity for treatment of type I allergy. DNA replicons display specific danger signals and offer an excellent safety profile based on apoptotic elimination of transfected host cells thereby preventing undesirable long-term expression of the transfected gene. Using the model allergen beta-Galactosidase in a protective approach, the results showed that a replicase-based DNA vaccine can induce a comparable immune response at a more than 1000-fold lower dose than a conventional DNA vaccine. DNA replicon doses as low as 10 ng significantly prevented from IgE induction by subcutaneous protein sensitization. Furthermore, in a therapeutic approach with the same construct, DNA replicons balanced an ongoing allergic response. These data were confirmed with a DNA replicon encoding the clinically relevant timothy grass pollen allergen Phl p 5. In addition, lung pathology could be prevented by pre-vaccination with DNA replicons as measured by the magnitude of eosinophilia, goblet cell hyperplasia, IL-5 production and proliferation of endothelial cells.