Article

Prevention and treatment of DNA vaccine encoding cockroach allergen Bla g 1 in a mouse model of allergic airway inflammation.

Department of Medicine, University of Tennessee Health Science Center, Memphis, USA.
Allergy (Impact Factor: 5.88). 09/2011; 67(2):166-74. DOI: 10.1111/j.1398-9995.2011.02727.x
Source: PubMed

ABSTRACT One-fourth of the US population is sensitized to the German cockroach. Primary German cockroach allergen Bla g 1 is detected in 63% of homes and 52% of childcare facilities in the United States. No effective treatment or vaccination strategies are yet available.
We evaluated the prophylactic and therapeutic efficacy of a plasmid DNA-mediated vaccination using the Bla g 1 gene in a mouse model of allergic inflammatory airway disease.
A plasmid DNA vector coding for the Bla g 1 allergen controlled by cytomegalovirus promoter was constructed. To estimate the protective efficacy, BALB/c mice were given three injections of plasmid DNA-Bla g 1 prior to sensitization with two priming doses of recombinant Bla g 1 (rBla g 1) antigens, followed by nebulized rBla g 1 challenge. In the therapeutic approach, sensitization was followed by administering Bla g 1 DNA vaccine.
Bla g 1 vaccination significantly reduced allergen-induced airway inflammation, even after mice were presensitized and a Th2-dominant response was established. The Bla g 1 vaccination significantly reduced total inflammatory cell infiltrate, eosinophilia, secretion of Th2 cytokines IL-4 and IL-5 in bronchoalveolar lavage fluid, allergen-induced inflammatory infiltrates in the lungs, and Bla g 1-specific IgE in serum upon challenge with rBla g 1. Importantly, Bla g 1 DNA vaccination was able to induce IL-10-secreting regulatory T cells that could suppress the allergen-specific Th2 cells.
DNA vaccination showed protective and therapeutic efficacy against a clinically relevant allergen Bla g 1.

0 Bookmarks
 · 
91 Views
  • Fresenius Environmental Bulletin 10/2013; 22(10):3048-3052. · 0.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1-R, seems to participate in obese-asthma phenotype in mice. OBJECTIVES: To evaluate the effect of a selective substance P receptor antagonist on a mouse model of diet-induced obesity and asthma. METHODS: Diet-induced obese Balb/c mice were sensitized and challenged with ovalbumin (OVA) and treated with a selective NK1-R antagonist or placebo. Serum glucose, insulin, IL-6, resistin, and OVA-specific IgE levels were quantified. A score for peribronchial inflammation in lung histology was used. Cells were counted in bronchoalveolar lavage fluid. Adipocyte sizes were measured. RESULTS: Ovalbumin-obese mice treated with NK1-R antagonist had lower weight (P = 0.0002), reduced daily food intake (P = 0.0021), reduced daily energy intake (P = 0.0021), reduced surface adipocyte areas (P < 0.0001), lower serum glucose (P = 0.04), lower serum insulin (P = 0.03), lower serum IL-(P = 0.0022), lower serum resistin (P = 0.0043), lower serum OVA-specific IgE (P = 0.035), and lower peribronchial inflammation score (P < 0.0001) than nontreated OVA-obese mice. We observed an interaction between obesity, allergen sensitization, and treatment with NK1-R antagonist for metabolic and systemic biomarkers, and for allergen sensitization and bronchial inflammation, showing a synergy between these variables. CONCLUSION & CLINICAL RELEVANCE: In an experimental model of obesity and asthma in mice, NK1-R blockade improved metabolic and systemic biomarkers, as well as allergen sensitization and bronchial inflammation. These positive effects support a common pathway in the obese-asthma phenotype and highlight SP as a target with potential clinical interest in the obese-asthma epidemics.
    Allergy 11/2012; · 5.88 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Immunology letters 02/2013; · 2.91 Impact Factor

Full-text

View
1 Download
Available from