The purpose of this study was to determine the in vivo desensitization efficacy of a hypoallergenic variant of egg white ovomucoid third domain (DIII) in Balb/c mice model. We mapped the immunodominant B-cell epitopes of ovomucoid in Balb/c mice. A hypoallergenic ovomucoid third domain (GMFA) mutant isoform having ablated allergenicity against egg allergic patient's sera was used to desensitize DIII-sensitized Balb/c mice by intraperitoneal injections. Ovomucoid DIII generated high levels of plasma histamine and specific immunoglobulin (Ig)E levels, and increased Th2 type cytokine (IL-4). On the other hand, the allergic response of mice desensitized with the GMFA was found to be significantly inhibited and abrogated by prevention of anaphylaxis reactions, low histamine levels and increased Th1-type cytokine (INF-γ). It was found that significantly higher levels of IL-10 and IL-12 were secreted in the desensitized group Desensitization with the GMFA antigen also suppressed synthesis of DIII specific-IgE levels and enhanced specific IgG2a and IgG levels compared with the group treated with the DIII antigen. The present results indicated that hyposensitization with the GMFA can desensitize or down-regulate the allergic response in Balb/c mice and this hypoallergenic variant of ovomucoid DIII can shift an ongoing allergen-specific Th2 response towards a Th1 skewed response.