| Approximately 5 million Americans (6 to 8% of children and 4% of adults) are known to suffer from food-induced allergic reactions. One of the most common food allergens is the egg. Ovomucoid is a dominant allergen in the egg-white and is comprised of three domains. Modulation of the immune response represents an excellent approach for the treatment of food-induced allergic reactions. The goal of this research was to investigate the role of N-linked glycan moieties of ovomucoid third domain (DIII) in IgE binding reactivity and to evaluate the efficacy of a genetic variant of ovomucoid DIII in suppression of egg-induced allergic reactions.; In order to analyze the role of N-linked glycan moieties of ovomucoid D111 in IgE binding, the gene encoding the ovomucoid DIII fragment was expressed in a Pichia pastoris expression system and the recombinant glycosylated ovomucoid (P-Gly) was characterized for its allergenicity, in comparison to the native ovomucoid with the carbohydrate chain (DIII+) in a Balb/c mouse model system. P-Gly showed a significant reduction of allergen-specific IgE levels in vivo with low amounts of interleukin-4 and increased interferon-gamma levels in vitro. However, upon induction of the intact ovomucoid-specific allergic response in mice, P-Gly ovomucoid did not desensitize the allergic response, indicating that N-linked glycan moieties may be important for suppression of specific IgE production, but were not ideal candidates for immunotherapeutic treatment of egg-induced allergic reactions.; Engineered hypoallergens with reduced reactivity for IgE antibodies are being examined to modulate the allergic response and develop prophylactic allergen vaccines. In the present study, we investigated the efficacy of a genetic variant of ovomucoid DIII (GMFA) to modulate the allergic response in mice. The immune response of GMFA in Balb/c mice revealed that IgE levels were reduced significantly with a decrease in levels of IL-4 and increase in levels of IFN-gamma in cultured lymphocytes. Desensitization with GMFA in ovomucoid-sensitized mice, significantly decreased allergic symptoms and histamine levels, suppressed production of ovomucoid-specific IgE, and modulated the T cell response, when compared to a control group treated with intact ovomucoid. This study indicates that GMFA will potentially provide targeted immunotherapy for egg-allergic patients. |
