Lit-LAMP-DNA-vaccine for shrimp allergy prevents anaphylactic symptoms in a murine model.

Abstract

Allergen-specific immunotherapy (AIT) is a promising therapeutic approach to food allergy but requires optimization in terms of both efficacy and safety due to the risk of undesired anaphylactic reactions. Here, we investigated the potential of a single DNA plasmid vaccine (Lit-LAMP-DNA-vaccine) encoding multivalent shrimp antigens (Lit v (Litopenaeus vannamei; Whiteleg shrimp) 1, Lit v4, and Lit v3) and a lysosomal-associated membrane protein (LAMP) as the next generation of AIT for patients with allergy. We first confirmed the expression of the LAMP-1-Lit v1-Lit v4-Lit v3 fusion protein in human cells transfected with the Lit-LAMP-DNA-vaccine, and the induction of anti-Lit v1, Lit v3, and Lit v4 IgG2a antibody production as well as Th1 response in Lit-LAMP-DNA-vaccine-treated mice. Next, we established an anaphylaxis model in mice epicutaneously sensitized with a crude shrimp protein extract (SPE) and investigated both the efficacy of Lit-LAMP-DNA-vaccine, and the difference in the mechanism of action (MOA) from oral immunotherapy (OIT). In the mouse shrimp allergy model, Lit-LAMP-DNA-vaccine potently suppressed anaphylactic reactions and mast cell activation with robust antigen-specific IgG2a production. The IgG1:IgG2a ratio was significantly lower than that of OIT. This suppressive effect was also confirmed by plasma transfer from mice previously vaccinated with the Lit-LAMP-DNA-vaccine. These results suggest that this Lit-LAMP-DNA-vaccine may represent a promising therapeutic strategy for human shrimp allergy which acts via the efficient induction of antigen-specific IgG with antagonism.