Oral and subcutaneous immunotherapy in a peanut allergy mouse model

L Wagenaar, M M Vonk, M Van Roest, L J W Kruijssen, L M J Knippels, B C A M Van Esch, R H H Pieters, J J Smit

    Research output: Chapter in Book/Report/Conference proceedingChapterAcademic

    Abstract

    Background: Although the prevalence of food allergy is increasing, no curative treatment is available yet. Human studies have shown encouraging suppression of food allergy by either subcutaneous or oral allergen-specific immunotherapy (IT). However, this therapy is still hampered by serious side effects and a lack of long-term tolerance. Improving the efficacy and safety of oral and subcutaneous immunotherapy (OIT and SCIT) is therefore necessary before widespread application. The NUTRALL consortium aims at developing knowledge-based immunotherapy protocols with improved efficacy and safety using dietary adjuvants. Method: In the present study, a C3H/ HeOuJ mouse model for intragastric induced peanut allergy was used to study the efficacy, mechanism of action and the dose responsiveness of OIT and SCIT. We looked at clinical efficacy (acute allergic skin responses, anaphylactic shock symptoms and body temperature), antibody and cytokine production and number of various immune cells after IT of sensitized mice. After sensitization, mice were treated with three different doses of peanut via the intragastric (5 times/week, OIT) or subcutaneous route (3 times/week, SCIT) for three consecutive weeks. Hereafter, mice were exposed to peanut via an intradermal, intragastric and intraperitoneal challenge. Results: Both SCIT and OIT were able to lower the acute allergic skin response, anaphylactic symptoms and mast cell degranulation after peanut exposure. In addition, serum levels of IgG1 and IgG2a, next to serum levels of IgE, were raised after both IT regimes. Furthermore, OIT prevented the increase of IgE after allergen challenge. The production of cytokines IL-5 and IL-10 was elevated after SCIT and allergen challenge, but not after OIT. IL-13 and IFN-γ production did not differ between the groups. Despite the observed changes in clinical parameters and antibody levels, the number of regulatory T cells, Th1 cells and Th2 cells in the spleen were not changed. Activated CD8-positive T cells were elevated after both SCIT and OIT, while activated CD4-positive T cells were only elevated in the SCIT groups. Conclusion: These data show that in a mouse model for peanut allergy, both SCIT and OIT protect against allergic and anaphylactic responses. Furthermore, we show that IT induced IgG1 and IgG2a and OIT prevented the increase of IgE after challenge. In future experiments, we will investigate whether dietary adjuvants improve the efficacy and/or safety of OIT and SCIT.
    Original languageEnglish
    Title of host publicationAllergy: European Journal of Allergy and Clinical Immunology
    Pages200
    Number of pages1
    Publication statusPublished - 2015

    Publication series

    NameAllergy: European Journal of Allergy and Clinical Immunology
    Volume70

    Keywords

    • CD4 antigen
    • CD8 antigen
    • European
    • T lymphocyte
    • Th1 cell
    • Th2 cell
    • adjuvant
    • allergen
    • allergy
    • anaphylaxis
    • antibody
    • blood level
    • body temperature
    • clinical immunology
    • cytokine
    • cytokine production
    • exposure
    • food allergy
    • human
    • immunocompetent cell
    • immunoglobulin E
    • immunotherapy
    • interleukin 10
    • interleukin 5
    • intragastric drug administration
    • intraperitoneal drug administration
    • mast cell degranulation
    • mouse
    • mouse model
    • parameters
    • peanut
    • peanut allergy
    • prevalence
    • regulatory T lymphocyte
    • safety
    • sensitization
    • side effect
    • skin
    • spleen
    • subcutaneous immunotherapy
    • therapy

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