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Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy

Nature Medicine volume 5, pages 387–391 (1999)Cite this article

Abstract

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.

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Figure 1: Appearance and size distribution of DNA nanoparticles.
Figure 2: β-galactosidase expression in mouse stomach and small intestine 5 days after oral delivery of DNA nanoparticles.
Figure 3: Antibody responses of immunized and control mice.
Figure 4: Anaphylactic response of mice after Arah2 challenge.
Figure 5: Histamine levels and vascular leakage after sensitization and challenge.

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Acknowledgements

We thank J. Lin and Q.-F. Wang for technical help with assays, and G. Bannon and W. Burks for providing the Arah2 cDNA, peanut extracts and recombinant Arah2 allergen. We also acknowledge the support of H.A. Sampson. This study was partially supported by NIH grant CA68011 to K.W.L. and NIH grants AI40274 and AI34002 to S.K.H.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Krishnendu Roy, Hai-Quan Mao & Kam W. Leong

  2. Department of Medicine, Johns Hopkins Allergy & Asthma Center, Johns Hopkins University School of Medicine, Baltimore , 21224, Maryland, USA

    Shau -Ku Huang

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  1. Krishnendu Roy
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Correspondence to Kam W. Leong.

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Roy, K., Mao, HQ., Huang, SK. et al. Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat Med 5, 387–391 (1999). https://doi.org/10.1038/7385

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