DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in mice

Allergen‐independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

“…It should be noted that while ISS-ODN treatment inhibited allergenchallenge induced IgE and IgG1 production modestly, only trace amounts of IgE are required to fully arm basophilic cells for allergen induced degranulation. 10,19,20 Therefore, we consider it likely that ISS-ODN inhibited the activities of basophilic cells in the nasal mucosa by additional mechanisms. We and others have previously shown that murine mast cells express Toll-like receptor-9 and produce cytokines in response to ISS-ODN stimulation but that ISS-ODN activation does not directly inhibit mast cell degranulation.…”

“…Fifteen min after the final OVA challenge, the frequency of sneezing and nasal rubbing events (four repetitive nasal rubbing movements equalled one event) were recorded for each OVA specific immune parameters Serum samples were collected from mice 1 day before the first OVA challenge and at the time of death, for OVA-specific immunoglobulin G1 (IgG1), IgG2a, and IgE determinations, as previously described. 10,11 For IgE analyses, sera were first mixed with a 50% slurry of protein G-sepharose beads (Pharmacia, Piscataway, NJ) to remove IgG and improve OVA-specific IgE detection sensitivity. Samples were then added to OVA-coated ELISA plates along with serial dilutions of a high titre OVA IgE standard.…”

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

“…In contrast, after subsequent aerosol challenge the IgE Ab titers were not significantly different from those of untreated control mice, although profound effects on eosinophil infiltration in the airways and local cytokine production were observed. By preventive DNA immunization with naked plasmid DNA IgE Ab production was inhibited in a number of studies, 7,8,[12][13][14][15][16] whereas effective therapeutic treatment of pre-existing IgE Ab responses with plasmid DNA was achieved by three groups only. 7,14,15 The reason for successful inhibition of pre-existing IgE responses may have been that Raz et al 7 used a relatively weak immunization protocol for priming, while Maecker et al 14 vaccinated with an allergen-IL-18 fusion DNA construct to enhance the efficiency of vaccination.…”

“…In different animal models, allergen genes have been transferred into the host using various routes, eg as 'naked' plasmid DNA by intramuscular or intradermal injection [7][8][9][10][11][12][13][14][15] or by ballistic transfection with the gene gun, 12,16 as plasmid DNA-polymer complexes by oral delivery, 17 or by means of recombinant mycobacteria as gene vector. 18 Prophylactic DNA immunization lead to inhibition of IgE Ab production 7,8,[12][13][14][15][16] and anaphylactic hypersensitivity, 13,16 as well as decreased airway hyperresponsiveness. 8,14 Induction of CD8 + T cells, as well as a shift towards a Th1 immune response contributed to this effect.…”

“…8,14 Induction of CD8 + T cells, as well as a shift towards a Th1 immune response contributed to this effect. 7,8,13,14,19,20 However, successful curative allergen gene transfer for the suppression of already established IgE Ab immune responses was reported only by three groups, 7,14,15 rendering it likely to improve therapeutic DNA vaccination by gene transfer with more efficient vehicles.…”