Mucosal expression of DEC-205 targeted allergen alleviates an asthmatic phenotype in mice

Abstract

Considering the rising incidence of allergic asthma, the symptomatic treatments that are currently applied in most cases are less than ideal. Specific immunotherapy is currently the only treatment that is able to change the course of the disease, but suffers from a long treatment duration. A gene based immunization that elicits the targeting of allergens towards dendritic cells in a steady-state environment might have the potential to amend these difficulties. Here we used a replication deficient adenovirus to induce the mucosal expression of OVA coupled to a single-chain antibody against DEC-205. A single intranasal vaccination was sufficient to mitigate an OVA-dependent asthmatic phenotype in a murine model. Invasive airway measurements demonstrated improved lung function after Ad-Dec-OVA treatment, which was in line with a marked reduction of goblet cell hyperplasia and lung eosinophilia. Furthermore OVA-specific IgE titers and production of type 2 cytokines were significantly reduced. Together, the here presented data demonstrate the feasibility of mucosal expression of DEC-targeted allergens as a treatment of allergic asthma.

IL-1β as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses

“…Nevertheless, to exclude severe lung injury and impaired gas exchange, we measured the lung function via forced oscillation technique with inhalation of escalating doses of the bronchoconstrictor methacholine as an aerosol. 39 None of the tested doses of rAd-IL-1β resulted in an increase of airway resistance, tissue damping or tissue elastance (Fig. 6) compared to non-vaccinated animals.…”

DNA and mRNA vaccination against allergies

“…Besides targeting subcellular compartments, efforts have been made to generate DNA vaccines that express proteins targeted to DCs with the aim to enhance specific immune responses (reviewed in). With respect to allergy DNA vaccines, recent studies found that targeting an allergen to DCs by encoding DEC‐205 fusion proteins alleviates allergic asthma in mice . Interestingly, although non‐targeted allergen also protected from sensitization 37 , the latter was associated with a TH1 phenotype, while DC targeted vaccination induced reduced levels of IFN‐γ production but was associated with elevated numbers of CD4 + CD25 + FoxP3 + T cells.…”

“…With respect to allergy DNA vaccines, recent studies found that targeting an allergen to DCs by encoding DEC‐205 fusion proteins alleviates allergic asthma in mice . Interestingly, although non‐targeted allergen also protected from sensitization 37 , the latter was associated with a TH1 phenotype, while DC targeted vaccination induced reduced levels of IFN‐γ production but was associated with elevated numbers of CD4 + CD25 + FoxP3 + T cells. Surprisingly, both TH‐1 as well as regulatory T‐cell induction were equally efficient in suppressing allergic lung inflammation, highlighting that multiple mechanisms can confer allergy protective immune responses after DNA immunization.…”

The Role of Lectin Receptors and Their Ligands in Controlling Allergic Inflammation

“…Subsequently, this finding was exploited for the delivery of allergens by genebased immunization using an adenoviral delivery of single chain antibodies directed against DEC205 fused to OVA to target the allergen towards DCs. This treatment resulted in the efficient suppression of an allergic immune response (14).…”