Elucidation of a non-anaphylactic hypoallergen vaccine of Scylla paramamosain arginine kinase with reduced IgE reactivity but retained T-cell reactivity

Shellfish allergies affect about 10% of the Malaysian population and are the most common triggers of life-threatening anaphylactic reactions. Existing treatment for shellfish allergies is based on the pharmacological treatment of symptoms and generalized seafood avoidance, which do not meet the patient’s needs. Allergen immunotherapy is the only long-lasting treatment for allergies, but may cause serious adverse reactions in certain individuals due to the use of natural allergens. As no immunotherapy for shellfish allergy is available, we aim to uncover the potential use of a hypoallergen of arginine kinase from mud crab (Scylla paramamosain) as a safer alternative to shellfish immunotherapy from the aspects of allergenicity, T-cell reactivity and anaphylactic activity. The proposed research is built upon our past research experience in successfully immuno-characterizing various hypoallergens. Basically, this will be achieved by the generation of four hypoallergen variants of mud crab arginine kinase (Scy p 2) using a combination of genetic and chemical modifications to remove both linear and conformational immunoglobulin-E epitopes. These variants will be then characterized in vitro using blood samples from crab-allergic individuals in terms of reduction in allergenicity (IgE binding and cross-linking) and retained immunogenicity (T-cell reactivity) compared to wild-type allergen. Next, two hypoallergens with the lowest IgE reactivity but maintained T-cell reactivity will be used as immunotherapy treatment in crab-allergic mice models to evaluate the absence of anaphylaxis, increase in arginine kinase specific IgG:IgE antibodies and an increase ratio of splenic Th1:Th2 cytokines compared to control mice. The expected outcome of this project is the development of a non-anaphylactic hypoallergen of Scylla paramamosain arginine kinase with reduced IgE reactivity but retained T-cell reactivity, which can be safely used against shellfish allergies.