Prevention of allergy by virus-like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model.

BACKGROUND: In high-risk populations, allergen-specific prophylaxis could protect from sensitization and subsequent development of allergic disease. However, such treatment might itself induce sensitization and allergies, thus requiring hypo-allergenic vaccine formulations. We here characterized the preventive potential of virus-like nanoparticles (VNP) expressing surface exposed or shielded allergens.

METHODS: Full-length major mugwort pollen allergen Art v 1 was selectively targeted either to the surface or to the inner side of the lipid bilayer envelope of VNP. Upon biochemical and immunological analysis, their preventive potential was determined in a humanized mouse model of mugwort pollen allergy.

RESULTS: VNP expressing shielded version of Art v 1, in contrast to those expressing surface-exposed Art v 1, were hypo-allergenic since they hardly induced degranulation of rat basophil leukemia cells sensitized with Art v 1-specific mouse or human IgE. Both VNP versions induced proliferation and cytokine production of allergen-specific T cells in vitro. Upon intranasal application in mice, VNP expressing surface-exposed but not shielded allergen, induced allergen-specific antibodies, including IgE. Notably, preventive treatment with VNP expressing shielded allergen protected mice from subsequent sensitization with mugwort pollen extract. Protection was associated with a Th1/Treg-dominated cytokine response, increased Foxp3+ Treg numbers in lungs and reduced lung resistance when compared to mice treated with empty particles.

CONCLUSION: VNP represent a novel and versatile platform for the in vivo delivery of allergens to selectively target T cells and prevent allergies without inducing allergic reactions or allergic sensitization. This article is protected by copyright. All rights reserved.