560
Adjuvant-Driven Redirection of Th2 Immunity Inhibits Allergic Reactions in Murine Models of Food Allergy
Sunday, March 5, 2017: 2:30 PM
Thomas B. Murphy Ballroom 2 (Georgia World Congress Center, Building B)
Jessica J. O'Konek, PhD, , , ,
Rationale:  Food allergy is most often the result of Th2-skewed immune responses with the production of allergen-specific IgE antibodies. Immunotherapies for food allergies generally require prolonged allergen exposure and have desensitized patients but have not induced long-lasting suppression of Th2 phenotypic responses or tolerized to allergens. We have previously demonstrated that a nanoscale emulsion (NE) adjuvant induces robust IgA and IgG antibody responses and Th1/Th17-polarized cellular immunity and can suppress pre-existing Th2 biased immunity. We now hypothesized that the redirection of Th2 immunity towards Th1/Th17 by nanoemulsion has the potential to balance the T cell response to allergen and modulate allergic immune responses.

Methods: Mice were sensitized to peanut or egg proteins to induce a Th2 and IgE allergic phenotype followed by three monthly intranasal immunizations with allergen and adjuvant.  Mice were then challenged with allergen, and symptoms of allergic reactions were measured.

Results:  Therapeutic intranasal immunizations resulted in decreased Th2 cytokines and IgG1 and IgE, as well as increased Th1/Th17 immune responses. Importantly, following allergen challenge, mice that received the allergy vaccines showed significant reductions in allergic hypersensitivity and anaphylaxis, including decreases in mast cell degranulation and inflammation.  Additionally, the immunization significantly increased IL-10 production as well as regulatory T cells, suggesting a mechanism for the suppression of Th2 immunity.

Conclusions:   Induction of Th1/Th17 immunity can suppress Th2 allergic responses, likely through IL-10 associated regulatory cells, and protect against anaphylaxis. This modification of allergen-specific immune responses may induce memory and cause more long-lived suppression of allergy than desensitization.