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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:124

Article

Behnecke, Anne¹  Li, Wei¹  Chen, Ling¹  Saxon, Andrew¹  Zhang, Ke¹ 

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Hart & Louise Lyon Immunol Lab, Div Pulm Crit Care & Clin Immunol Allergy,Sect Cl, Los Angeles, CA 90095 USA

关键词: Gene vaccination;    human IgE;    dendritic cells;    food allergy;    IgE high-affinity receptor;   

DOI  :  10.1016/j.jaci.2009.03.020

来源: Elsevier

【 摘 要 】

Background: 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. Objective: We sought to construct a genetically engineered human E-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. Methods: Genetic engineering was used to design and produce the EPL fusion gene, consisting of the human CH epsilon 2-4 linked to 55 lysine residues, and the conventional approaches were used to characterize the biologic features of EPL. Results: 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. Conclusion: 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. (J Allergy Clin Immunol 2009;124:108-13.)

【 授权许可】

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