A novel vaccination platform for epicutaneous allergen-specific immunotherapy based on beta-glucan neoglycoconjugates

Abstract

Abstract Coupling of long chain carbohydrates to allergens can mask IgE epitopes and thus reduce the allergenicity of the neoglycoconjugates. The resulting molecules can target and activate dendritic cells via C-type lectin receptors. Neoglycoconjugates therefore have a high potential for epicutaneous immunotherapy (EPIT) by delivering a hypoallergenic vaccine to a tissue rich in dendritic cells. In the current study we test the therapeutic efficiency of the beta-glucan laminarin conjugated to ovalbumin (LamOVA) in a mouse model of allergic asthma. Sensitized Balb/C mice were treated epicutaneously via micropores created by fractional laser ablation. Humoral and cellular responses were evaluated by ELISA, RBL assay and BAT. Lung function was analyzed by whole body plethysmography. Laminarin remained biologically active after coupling to ovalbumin as indicated by binding to Dectin-1 receptor. IgE epitopes were successfully masked according to in vitro IgE binding aasay and skin reaction scores in therapeutic setup.LamOVA was more potent in stimulating humoral immune responses in comparison to OVA and induced the highest IgG1 and IgG2a production. Epicutaneous treatment with OVA and LamOVA reduced lung inflammation and improved lung function of sensitized mice more efficiently compared to s.c. injection with OVA/alum. Epicutaneous immunotherapy can alleviate lung inflammation and reduce airway hyperresponsiveness in sensitized mice more efficiently than s.c. injection with alum. Coupling of allergen to laminarin reduces local side effects and increases the immunogenicity, resulting in a safer therapy.