Genetic Vaccines and Therapy

Background: Allergen-induced imbalance of specific T regulatory (Treg) cells and T helper 2 cells plays a decisive role in the development of immune response against allergens. Objective: To evaluate effects and potential mechanisms of DNA vaccine containing ovalbumin (OVA) and Fc fusion on allergic airway inflammation. Methods: Bronchoalveolar lavage (BAL) levels of inflammatory mediators and leukocyte infiltration, expression of CD11cCD80 and CD11cCD86 co-stimulatory molecules in spleen dendritic cells (DCs), circulating CD4 and CD8 T cells, Foxp3+ in spleen CD4 T cells and spleen CD4 T cells were measured in OVA-sensitized and challenged animals pretreated with pcDNA, OVA-pcDNA, Fc-pcDNA, and OVA-Fc-pcDNA. Results: OVA-Sensitized and challenged mice developed airway inflammation and Th2 responses, and decreased the proliferation of peripheral CD4and CD8 T cells and the number of spleen Foxp3 Treg. Those changes with increased INF-γ production and reduced OVA-specific IgE production were protected by the pretreatment with OVA-Fc-pcDNA. Conclusion: DNA vaccine encoding both Fc and OVA showed more effective than DNA vaccine encoding Fc or OVA alone, through the balance of DCs and Treg. Introduction Allergic asthma is a Th2 lymphocyte-associated inflammatory airway disease characterized by airway eosinophilia, goblet-cell hyperplasia, variable airway obstruction and hyper-responsiveness [1]. The balance between allergen-specific T regulatory (Treg) cells and T helper 2 cells appears to be decisive in the development of the immune response against allergens [2]. Allergen-specific immunotherapy (SIT) has been suggested as one of the few antigen-specific treatments for inflammatory diseases, with a long-term of efficacy [2]. SIT could reduce the development of asthma and bronchial responses in patients exposed to inhaled allergens. It is possible to target anti-inflammatory therapy to the various pathways of the disease, improving asthma control. However, the mechanisms by which allergen-DNA-targeted dentritic cells (DCs) plays anti-inflammatory roles remain unclear. We found that allergen-DNA-targeted DCs reduced Th2 responses and the expression of C co-stimulatory molecules like D11cCD80 and CD11cCD86 in experimental asthma [3]. The present study furthermore investigated the potential mechanisms where Treg cells and spleen DCs may be involved in the therapeutic process of DNA vaccination coding with Fc and ovalbumin (OVAFc-DNA) in in allergic models. We determine the therapeutic role of immunization with OVA-Fc-DNA-targeted DCs and ascertain the roles of spleen DCs in the protection.