IgE-mediated allergen gene vaccine platform targeting human antigen-presenting cells through the high-affinity IgE receptor.
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 epsilon-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 CHepsilon2-4 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.


CONCLUSIONS
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.
Hart and Louise Lyon Immunology Laboratory, Section of Clinical Immunology/Allergy, Division of Pulmonary, Critical Care and Clinical Immunology/Allergy, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Anne
A
Behnecke
Wei
W
Li
Ling
L
Chen
Andrew
A
Saxon
Ke
K
Zhang
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003888:Desensitization, Immunologic; D016503:Drug Delivery Systems; D006801:Humans; D007073:Immunoglobulin E / Q000627:therapeutic use*; D051379:Mice; D011107:Polylysine / Q000235:genetics; D017455:Receptors, IgE / Q000187:drug effects*; D011994:Recombinant Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000494:pharmacology*
D017455:Receptors, IgE; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D011107:Polylysine; D007073:Immunoglobulin E