Optimization of a Der p 2-based prophylactic DNA vaccine against house dust mite allergy

Abstract

DNA vaccines encoding allergens are promising immunotherapeutics to prevent or to treat allergy through induction of allergen-specific Th1 responses. Despite anti-allergy effects observed in small rodents, DNA-based vaccines are weak immunogens in primates and humans and particularly when administered by conventional injection. The goal of the present study was to improve the immunogenicity of a prophylactic vaccine encoding the major house dust mite allergen Der p 2. In this context, we evaluated the influence of different DNA backbones including notably intron and CpG enriched sequence, the DNA dose, the in vivo delivery by electroporation as well as the heterologous prime boost regimen on the vaccine efficiency. We found that a minimal allergen expression level threshold must be reached to induce the production of specific antibodies but beyond this limit, the intensity of the immune response was independent on the DNA dose and allergen expression. The in vivo DNA delivery by electroporation drastically enhanced the production of specific antibodies but not the IFNg secretion. Vaccination of naïve mice with DNA encoding Der p 2 delivered by electroporation even at very low dose (2μg) prevented the development of house dust mite allergy through Th1-skewed immune response characterized by the drastic reduction of allergen-specific IgE, IL-5 and lung inflammation together with the induction of strong specific IgG2a titers and IFNg secretion. CpG cassette in the DNA backbone does not play a critical role in the efficient prophylaxis. Finally, comparable protective immune responses were observed when using heterologous DNA prime/protein boost or homologous DNA prime/boost. Taken together, these data suggest that the potent Th1 response induced by DNA-based vaccine encoding allergens through electroporation provides the rationale for the evaluation of DNA encoding Der p 2 into HDM allergy clinical trials.