Nanoemulsion adjuvant-driven redirection of TH2 immunity inhibits allergic reactions in murine models of peanut allergy

Jessica J O'Konek; Jeffrey J Landers; Katarzyna W Janczak; Rishi R Goel; Anna M Mondrusov; Pamela T Wong; James R Baker Jr

doi:10.1016/j.jaci.2018.01.042

Nanoemulsion adjuvant-driven redirection of T_H2 immunity inhibits allergic reactions in murine models of peanut allergy

J Allergy Clin Immunol. 2018 Jun;141(6):2121-2131. doi: 10.1016/j.jaci.2018.01.042. Epub 2018 Apr 11.

Authors

Jessica J O'Konek¹, Jeffrey J Landers², Katarzyna W Janczak², Rishi R Goel², Anna M Mondrusov², Pamela T Wong², James R Baker Jr³

Affiliations

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.

PMID: 29655584
DOI: 10.1016/j.jaci.2018.01.042

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 T_H17-polarized immunity, as well as systemic T_H1-biased cellular immunity with suppression of pre-existing T_H2-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 T_H2 cytokine, IgG₁, and IgE levels, whereas T_H1 and mucosal T_H17 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 T_H17 and systemic T_H1-biased immunity can suppress T_H2-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.

Keywords: Food allergy; adjuvant; allergen immunotherapy; allergic disease; intranasal immunization; nanoemulsion; peanut allergy.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adjuvants, Immunologic / administration & dosage*
Administration, Intranasal
Animals
Desensitization, Immunologic / methods*
Disease Models, Animal
Emulsions
Female
Mice
Nanoconjugates / administration & dosage
Peanut Hypersensitivity / immunology*
Th2 Cells / drug effects
Th2 Cells / immunology*

Substances

Adjuvants, Immunologic
Emulsions
Nanoconjugates