IgE-mediated allergen gene vaccine platform targeting human antigen-presenting cells through the high-affinity IgE receptor

• Published in: Journal of allergy and clinical immunology Vol. 124; no. 1; pp. 108 - 113
• Main Authors: Behnecke, Anne, Li, Wei, Chen, Ling, Saxon, Andrew, Zhang, Ke
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2009; Elsevier; Elsevier Limited
• Subjects: Allergens; Allergic diseases; Allergies; Allergy and Immunology; Animals; Antigen-presenting cells; Antigen-Presenting Cells - drug effects; Biological and medical sciences; Blotting, Western; CHO Cells; Cricetinae; Cricetulus; dendritic cells; Deoxyribonucleic acid; Desensitization, Immunologic; Digestive allergic diseases; DNA; DNA vaccines; Drug Delivery Systems; Food allergies; food allergy; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene expression; Gene vaccination; Genetic engineering; human IgE; Human subjects; Humans; IgE high-affinity receptor; Immunoglobulin E; Immunoglobulin E - therapeutic use; Immunopathology; Ligands; Medical sciences; Mice; Polylysine - genetics; Protein expression; Proteins; Receptors, IgE - drug effects; Recombinant Proteins - immunology; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Vaccines; Vaccines, DNA - pharmacology; EPL; GFP; PLL; NP; dendritic cells; APC; human IgE; Gene vaccination; CHO; IgE high-affinity receptor; food allergy; DC; Dendritic cell; 4-hydroxy-3-nitrophenacetyl; Poly-L-lysine; Chinese hamster ovary; Green fluorescent protein; Antigen-presenting cell; ϵ-Polylysine; Human; Food allergy; Immunopathology; Targeting; IgE; Vaccination; Vaccine; Prevention; Immunology; Gene; Antigen presenting cell; Digestive diseases; Affinity; Genetics; Allergen; Biological receptor
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2009.03.020

Treatment of IgE-mediated food allergy with standard protein-based allergen immunotherapy has proved both unsuccessful and hazardous. Allergen gene vaccination represents a promising alternative, but difficulties in gene targeting and expression in antigen-presenting cells represent a major limitation for efficient gene vaccination. We sought to construct a genetically engineered human ε-polylysine (EPL) fusion protein that binds allergen gene expression systems and targets the gene vaccine complex to antigen-presenting cells through the interaction of EPL and the high-affinity receptor for IgE for efficient allergen gene vaccination. Genetic engineering was used to design and produce the EPL fusion gene, consisting of the human CHε2-4 linked to 55 lysine residues, and the conventional approaches were used to characterize the biologic features of EPL. EPL was assembled as functional dimers and capable of binding DNA plasmids in both an EPL protein and plasmid DNA concentration–dependent manner. EPL targeted plasmid DNA to the high-affinity receptor for IgE on cell surfaces and increased the model gene uptake/expression. The EPL-DNA complexes were shown not to trigger mast cell degranulation. EPL is able to function as a gene carrier system to target allergen gene to the high-affinity receptor for IgE-expressing cells through ligand receptor–mediated interactions.