Oral gene delivery with chitosan--DNA nanoparticles generates immunologic protection in a murine model of peanut allergy.
Food allergy is a common and often fatal disease with no effective treatment. We describe here a new immunoprophylactic strategy using oral allergen-gene immunization to modulate peanut antigen-induced murine anaphylactic responses. Oral administration of DNA nanoparticles synthesized by complexing plasmid DNA with chitosan, a natural biocompatible polysaccharide, resulted in transduced gene expression in the intestinal epithelium. Mice receiving nanoparticles containing a dominant peanut allergen gene (pCMVArah2) produced secretory IgA and serum IgG2a. Compared with non-immunized mice or mice treated with 'naked' DNA, mice immunized with nanoparticles showed a substantial reduction in allergen-induced anaphylaxis associated with reduced levels of IgE, plasma histamine and vascular leakage. These results demonstrate that oral allergen-gene immunization with chitosan-DNA nanoparticles is effective in modulating murine anaphylactic responses, and indicate its prophylactic utility in treating food allergy.
Roy
K
K
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mao
H Q
HQ
Huang
S K
SK
Leong
K W
KW
D055516:2S Albumins, Plant; D000284:Administration, Oral; D000707:Anaphylaxis / Q000276:immunology / Q000628:therapy*; D000818:Animals; D000906:Antibodies / Q000097:blood; D052179:Antigens, Plant; D010367:Arachis / Q000235:genetics / Q000276:immunology*; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D048271:Chitosan; D018744:DNA, Plant / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015870:Gene Expression; D017343:Genes, Plant; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000032:analysis; D051379:Mice; D008806:Mice, Inbred AKR; D010316:Particle Size; D010940:Plant Proteins; D014170:Transformation, Genetic; D019444:Vaccines, DNA / Q000627:therapeutic use*
D055516:2S Albumins, Plant; D000906:Antibodies; D052179:Antigens, Plant; C078642:Ara h II protein, Arachis hypogaea; D018744:DNA, Plant; D006023:Glycoproteins; D010940:Plant Proteins; D019444:Vaccines, DNA; D002686:Chitin; D007073:Immunoglobulin E; D006632:Histamine; D048271:Chitosan