Jessica J O'Konek1, Jeffrey J Landers2, Katarzyna W Janczak2, Rishi R Goel2, Anna M Mondrusov2, Pamela T Wong2, James R Baker3. 1. Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich. Electronic address: jjoz@umich.edu. 2. Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich. 3. Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Mich. Electronic address: jbakerjr@umich.edu.
Abstract
BACKGROUND: Immunotherapy for food allergies involves progressive increased exposures to food that result in desensitization to food allergens in some subjects but not tolerance to the food. Therefore new approaches to suppress allergic immunity to food are necessary. Previously, we demonstrated that intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal antibody and TH17-polarized immunity, as well as systemic TH1-biased cellular immunity with suppression of pre-existing TH2-biased immunity. OBJECTIVE: We hypothesized that immunization with food in conjunction with the nanoemulsion adjuvant could lead to modulation of allergic reactions in food allergy by altering pre-existing allergic immunity and enhancing mucosal immunity. METHODS: Mice were sensitized to peanut with aluminum hydroxide or cholera toxin. The animals were then administered 3 monthly intranasal immunizations with peanut in the nanoemulsion adjuvant or saline. Mice were then challenged with peanut to examine allergen reactivity. RESULTS: The NE intranasal immunizations resulted in marked decreases in TH2 cytokine, IgG1, and IgE levels, whereas TH1 and mucosal TH17 immune responses were increased. After allergen challenge, these mice showed significant reductions in allergic hypersensitivity. Additionally, the NE immunizations significantly increased antigen-specific IL-10 production and regulatory T-cell counts, and the protection induced by NE was dependent in part on IL-10. Control animals immunized with intranasal peanut in saline had no modulation of their allergic response. CONCLUSIONS: NE adjuvant-mediated induction of mucosal TH17 and systemic TH1-biased immunity can suppress TH2-mediated allergy through multiple mechanisms and protect against anaphylaxis. These results suggest the potential therapeutic utility of this approach in the setting of food allergy.
BACKGROUND: Immunotherapy for food allergies involves progressive increased exposures to food that result in desensitization to food allergens in some subjects but not tolerance to the food. Therefore new approaches to suppress allergic immunity to food are necessary. Previously, we demonstrated that intranasal immunization with a nanoemulsion (NE) adjuvant induces robust mucosal antibody and TH17-polarized immunity, as well as systemic TH1-biased cellular immunity with suppression of pre-existing TH2-biased immunity. OBJECTIVE: We hypothesized that immunization with food in conjunction with the nanoemulsion adjuvant could lead to modulation of allergic reactions in food allergy by altering pre-existing allergic immunity and enhancing mucosal immunity. METHODS:Mice were sensitized to peanut with aluminum hydroxide or cholera toxin. The animals were then administered 3 monthly intranasal immunizations with peanut in the nanoemulsion adjuvant or saline. Mice were then challenged with peanut to examine allergen reactivity. RESULTS: The NE intranasal immunizations resulted in marked decreases in TH2 cytokine, IgG1, and IgE levels, whereas TH1 and mucosal TH17 immune responses were increased. After allergen challenge, these mice showed significant reductions in allergic hypersensitivity. Additionally, the NE immunizations significantly increased antigen-specific IL-10 production and regulatory T-cell counts, and the protection induced by NE was dependent in part on IL-10. Control animals immunized with intranasal peanut in saline had no modulation of their allergic response. CONCLUSIONS: NE adjuvant-mediated induction of mucosal TH17 and systemic TH1-biased immunity can suppress TH2-mediated allergy through multiple mechanisms and protect against anaphylaxis. These results suggest the potential therapeutic utility of this approach in the setting of food allergy.
Authors: Mohammad Farazuddin; Rishi R Goel; Nicholas J Kline; Jeffrey J Landers; Jessica J O'Konek; James R Baker Journal: Front Immunol Date: 2019-05-08 Impact factor: 7.561
Authors: Sanjay Rathod; Manda Ramsey; Mary V Relling; Fred D Finkelman; Christian A Fernandez Journal: Haematologica Date: 2018-09-20 Impact factor: 9.941
Authors: Mohammad Farazuddin; Jeffrey J Landers; Katarzyna W Janczak; Hayley K Lindsey; Fred D Finkelman; James R Baker; Jessica J O'Konek Journal: Front Immunol Date: 2021-02-25 Impact factor: 7.561
Authors: Kevin R Hughes; Michael N Saunders; Jeffrey J Landers; Katarzyna W Janczak; Hamza Turkistani; Laila M Rad; Stephen D Miller; Joseph R Podojil; Lonnie D Shea; Jessica J O'Konek Journal: Front Allergy Date: 2022-02-07