Abstract
Allergen specific immunotherapy (AIT) can modulate the allergic response causing a long-term symptom subsidence/abolishment which leads to reduced drug use and prevention of new sensitization. AIT of house dust mite allergy (HDM) using the mite crude extract (CE) as the therapeutic agent is not only less effective than the AIT for many other allergens, but also frequently causes adverse effects during the treatment course. In this study, mouse model of Dermatophagoides pteronyssinus (Dp) allergy was invented for testing therapeutic efficacies of intranasally administered liposome (L) encapsulated vaccines made of single Dp major allergens (L-Der p 1, L-Der p 2), combined allergens (L-Der p 1 and Der p 2), and crude Dp extract (L-CE). The allergen sparing intranasal route was chosen as it is known that the effective cells induced at the nasal-associated lymphoid tissue can exert their activities at the lower respiratory tissue due to the common mucosal traffic. Liposome was chosen as the vaccine delivery vehicle and adjuvant as the micelles could reduce toxicity of the entrapped cargo. The Dp-CE allergic mice received eight doses of individual vaccines/placebo on alternate days. All vaccine formulations caused reduction of the Th2 response of the Dp allergic mice. However, only the vaccines made of single refined allergens induced expressions of immunosuppressive cytokines (TGF-β, IL-35 and/or IL-10) which are the imperative signatures of successful AIT. The data emphasize the superior therapeutic efficacy of single refined major allergen vaccines than the crude allergenic extract vaccine.
Highlights
House dust mites (HDM), Dermatophagoides pteronyssinus (Dp) and D. farinae (Df), produce a myriad of proteins and macromolecules that sensitize humans to allergic diseases including allergic dermatitis, allergic rhinitis and asthma worldwide [1]
There was no change in the serum IgE levels in the vaccinated and placebo mice after provocation (PP) compared with the pretreatment levels (BV)
Neutrophils were predominant cells infiltrated into the lungs of sham mice which should be due to nonallergy-related tissue irritation and perhaps partly due to endotoxin contained in the PBS that was used for intranasal challenge (20 μl/mouse) and nebulization (10 ml aerosolic PBS for 10 mice; it is not known how many EU of endotoxin were inhaled by individual mice)
Summary
House dust mites (HDM), Dermatophagoides pteronyssinus (Dp) and D. farinae (Df), produce a myriad of proteins and macromolecules that sensitize humans to allergic diseases including allergic dermatitis, allergic rhinitis and asthma worldwide [1]. Group 1 (Der p 1 and Der f 1) and group 2 (Der p 2 and Der f 2) allergens are the most abundant and immunodorminant as more than 80% of the mite allergic subjects have serum IgE specific to them [3,4,5,6]. The group 1 allergens are highly cross-reactive in terms of their ability to induce T cell response and serum IgE binding [7]. Their allergenicity is attributable to their cysteine protease activity [8,9]. Der p 2 and Der f 2 have approximately 87% sequence identity and they share tertiary structure [23]. IgE epitopes of the group 2 allergens are more dependent on the conformational structure than the linear sequences [26]
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