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

J Allergy Clin Immunol. 2009 Jul;124(1):108-13. doi: 10.1016/j.jaci.2009.03.020. Epub 2009 May 7.

Abstract

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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects*
  • Blotting, Western
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Desensitization, Immunologic*
  • Drug Delivery Systems*
  • Humans
  • Immunoglobulin E / therapeutic use*
  • Mice
  • Polylysine / genetics
  • Receptors, IgE / drug effects*
  • Recombinant Proteins / immunology
  • Vaccines, DNA / pharmacology*

Substances

  • Receptors, IgE
  • Recombinant Proteins
  • Vaccines, DNA
  • Polylysine
  • Immunoglobulin E