Overcoming Shellfish Allergy: How Far Have We Come?

Abstract

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a "cure "for shellfish allergy is within reach.

Keywords: DNA vaccine; allergen-specific immunotherapy; component-resolved diagnosis; diagnosis; tropomyosin.

Figure 1

Prevalence of shellfish allergy. The estimated rate of shellfish allergy (pink) in populations at different geographical areas based on (A) self-reports and (B) IgE sensitization. Percentage in purple indicates the prevalence of shellfish allergy based on oral food challenge results. Asterisk (*) indicates that only children and/or adolescent populations aged 18 years or below were included in the estimation of shellfish allergy prevalence.

Figure 2

Immunotherapeutic strategies for overcoming shellfish allergy. The applicability of unmodified tropomyosin as a sublingual immunotherapy (SLIT), hypoallergens constructed by high hydrostatic pressure processing, Maillard reaction, enzyme cross-linking and epitope manipulation, immunoregulatory peptides including T cell epitopes and mimotopes, as well as hypoallergen-encoding DNA vaccines has been investigated over the past years.

Figure 3

Experimental design of the hypoallergen-encoding DNA vaccine study. Two hypoallergens, MEM49 and MED171, of shrimp tropomyosin were constructed by epitope mutation and deletion, respectively. DNA vaccines were then constructed by cloning and expressing the hypoallergens in mammalian expression plasmids. Our data demonstrated that pMEM49 and pMED171 were effective in down-modulating shrimp tropomyosin-induced allergy in BALB/c mice, such as suppressing the Met e 1-specific IgE and inflammatory responses in the gut while increasing specific IgG_2a with inhibitory functions. Optimization of the vaccines would follow in constructing next-generation DNA vaccines with enhanced in vivo expression of the hypoallergen and immunogenicity of the vaccines. In vitro cell-based analyses involving the major immune players (e.g., dendritic cells, T and B cells) in human and mouse to dissect the modulatory mechanism of the hypoallergen-encoding DNA vaccines, as well as in vivo analyses in murine model for the safety and therapeutic efficacies of the vaccines are essential in addressing the applicability of the vaccines for the clinical treatment of shellfish allergy.