Surface Expression of Major Allergens on Plant-Made eBioparticle Combines Hypo-Allergenicity with Potent Immune Activation

Allergen immunotherapy is the only disease-modifying treatment for allergic diseases with proven sustained efficacy, but long treatment duration, chronic exposure to aluminum salts as well as allergic side-effects are major drawbacks. We hereby evaluate an innovative plant-based vaccine platform of in vivo assembled micro-sized bioparticles (BPs) expressing recombinant allergens for improved safety and immunogenicity. Human monocyte-derived dendritic cells (moDCs) were exposed to the major cat allergen Fel d 1 or the major house dust mite allergen Der p 2 and plant-made BPs displaying the respective allergen. MoDC maturation and cytokine expression was measured by flow cytometry as well as qPCR and ELISA, respectively. Hypo-allergenicity of allergen-displaying BPs was assessed by basophil degranulation assay using rat basophilic leukemia cells sensitized with Fel d 1- or Der p 2-specific human IgE. In contrast to the soluble allergens, plant-made BPs displaying Fel d 1 or Der p 2 induce strong maturation of moDCs and trigger potent IL-6, IL-10 and IL-12 responses. Notably, both Fel d 1 and Der p 2-displaying BPs were hypoallergenic with >300-fold and 10-fold reduced allergenicity, respectively. Multivalent high-density presentation of allergens on micro-sized plant-made BPs potently increases immunogenicity while significantly decreasing allergenicity compared to their poorly immunogenic soluble counterparts. By combining potent immune activation with hypo-allergenicity it may offer a safer alternative for rapid induction of protective immunity without addition of adjuvants like aluminum salts.