An Adjuvant-Free Mouse Model of Transdermal Sensitization and Oral Elicitation of Anaphylaxis to Shellfish

Abstract

Background: Shellfish (SF) allergy is a leading cause of systemic anaphylaxis in humans. An adjuvant-free mouse model to evaluate allergenicity and oral anaphylaxis to SF is currently unavailable. Here, we tested the hypothesis that transdermal exposure (TDE) to SF protein extract (SFPE) not only elicits a systemic allergic immune response but also will clinically sensitize mice for oral anaphylaxis. Methods: Adult BALB/c female mice (6-8 weeks of age) were exposed to saline or SFPE once a week for 4 weeks using a transdermal sensitization method. Systemic SF-specific IgE, IgG1 and IgG2a and total (t)IgE responses were measured using ELISA. Systemic anaphylaxis upon oral SFPE administration was assessed according to clinical symptoms and the hypothermia shock response (HSR). Using individual mouse data, the correlation between the readouts of allergenicity was determined using Pearson's analysis. Spleen-cell IL-4 and IFN-γ responses were determined using primary cell culture and ELISA. Results: TDE to SFPE resulted in marked systemic specific (s)IgE, tIgE, IgG1 and IgG2a responses. Oral challenge with SFPE in sensitized mice (but not controls) elicited systemic anaphylactic clinical reactions and HSR. A strong correlation was observed between sIgE, tIgE and HSR. Spleen cells isolated from allergic mice (but not controls) exhibited memory IL-4 and IFN-γ cytokine responses. Conclusion: We report a novel adjuvant-free mouse model of SF allergy with robust quantifiable and correlated readouts of allergenicity that may be used in basic biomedical, preclinical and applied food/nutrition research on SF allergy.

Enhanced Prophylactic and Therapeutic Effects of Polylysine-Modified Ara h 2 DNA Vaccine in a Mouse Model of Peanut Allergy

“…First, it is noteworthy that there are strain-dependent variations in the development of allergic responses among different mouse strains and the effect of DNA-based immunotherapy might be strain dependent and not universally effective in reversing IgE-mediated food hypersensitivity in human subjects [40]. Second, our peanut allergy model established in BALB/c mice is not through a physiological route of sensitization, and the usage of alum in the food allergy model is still in doubt because of its nonphysiological nature [41]. Furthermore, the recent expansion of the repertoire of therapeutic nucleic acids from classical DNA gene transfer constructs to many other gene expression and protein-modulating nucleic acids such as mRNA, miRNA, or siRNA is expected to generate an additional boost for further optimization of polymeric delivery systems.…”

Advances in Molecular Mechanisms of Wheat Allergenicity in Animal Models: A Comprehensive Review

“…In that sense, adjuvant-free models, such as skin sensitization models, reported for mouse and rats are desirable because data interpretation of the intrinsic allergenicity of wheat proteins becomes easier [38,48]. There are a number of adjuvant-free mouse models reported in the literature for tree nut, milk, sesame, and shellfish allergies [39,40,41,42,43,49,50]. Therefore, there is an exciting opportunity to develop novel adjuvant-free models for various types of wheat allergies.…”

Recent Advances in Experimental Allergy

“…Tools to study shellfish allergy are also continually being developed and refined. For example, an adjuvant-free mouse model for shellfish allergy was developed and clinical studies using the ImmunoCAP-FEIA technology highlighted the need for food challenge tests when diagnosing shrimp allergy [66, 67]. …”