Our results demonstrate significant decrease in the in vivo and in vitro IgE reactivity and allergenicity of the two designer shrimp tropomyosin hypoallergens MEM49 and MED171 when compared to the wild type allergen Met e 1 and more importantly, robust IgG antibodies’ responses with inhibitory potential to Met e 1-specific IgE antibodies of shrimp allergy subjects and Met e 1-sensitized mice. Here, IGHE is linked to allergic disease.