Evaluating the efficacy of BECC-derived adjuvants to skew allergen-specific immunotherapies 4262

Abstract Description Allergen-specific immunotherapy (AIT) is a therapeutic strategy that introduces escalating doses of allergic antigen to shift memory B cell populations from production of allergic IgE antibodies towards production of non-allergic antibody isotypes like IgG2. A limitation in the effectiveness of AIT is that the time to tolerization and effectiveness varies among individuals. Two novel lipid A mimetics, BECC 438 and BECC 470, developed through bacterial enzymatic combinatorial chemistry (BECC), have been shown to promote non-allergic Th1-skewed immune responses. We hypothesize that using BECC-derived adjuvants in AIT will allow for more reliable, robust, and rapid reduction in the production of IgE, leading to better allergic outcomes following antigen exposure. Using BALB/c mice in a model of ovalbumin (OVA)-induced allergic asthma, we find that mice sensitized with OVA+Alhydrogel, when compared to mice sensitized with OVA alone and PBS-treated mice, have increased markers of allergic airway inflammation. These results include higher IgE antibody levels, as measured by an antigen-specific indirect serum ELISA, and increased lung epithelial thickness, as observed in H&E-stained lung sections. Ongoing experiments measure these markers of allergic responses to antigen challenge after receiving AIT with or without BECC adjuvants. Integrating these adjuvants into AIT aims to enhance immune tolerance and reduce the burden of allergic responses on human health. Funding Sources This research was supported by a research training grant provided by the National Institute of General Medical Sciences (NIGMS) through The Bridges to the Doctorate Program, NIH/NIGMS 5T32GM146694-02; 5T32GM146694-03 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)