Due to the ethical concerns around performing challenge studies of potential food allergens in humans, animal models have been an attractive alternative for creating a standardized allergen exposure protocol in an easily available animal. The characterization and testing for sensitization to proteins is impossible to achieve in humans. Because of the challenges in working with humans in controlled studies, the goal of the animal model has been to predict whether a novel protein has the capacity to elicit IgE production in the animal and have some level of relevance to the human condition. Several models of allergen exposure have been attempted in multiple species, with each species having advantages over others. The rodent models offer the advantage of ease of handling, availability, and genetic stability. Rodents can be compared for their response to a variety of exposure sites40 and, due to the importance of genetic background, several different strains can be assessed for the relevance to the observed human sensitivity to a given allergen.41 In addition, rodents are useful in studying the mechanisms of allergy simply because of the vast array of reagents available to researchers. Although IgE binding is usually the parameter measured to indicate sen-sitization in animals, biomarkers of sensitization can be greatly expanded to include cytokines and cell receptors for rodent models. Alternatively, other species, such as the dog and swine models, offer closer approximations of human clinical symptoms. The swine, in particular, has been useful for describing sensitivity to various peanut allergens42 with strong correlations to human peanut allergy.
A validated, standardized model of allergy that simulates the sensitization process in humans remains difficult to perform because there is a lack of well defined allergic responses in animals that remain consistent among allergens and which correlate well with human allergy. For mechanistic studies on optimization of novel allergy vaccines, it is acceptable that the model reflects only important aspects of the human disease but not the natural sensitization process. However, for a predictive model, a very high correlation to the sensitization process taking place in man is required. Moreover, the preparation of allergens, the selection of adjuvant, and the timing between sensitization and allergen challenge remain difficult to determine for all but a few of the well-studied proteins. Furthermore, reproducibility across study sites of an animal model's response to even a well-characterized allergen, such as ovalbumin, remains elusive. Recent reviews on animal models bring to light considerations for improving animal models, such as including proper negative and positive study controls, standardizing allergen preparations, and selecting the study animal and the appropriate genetic strain.43-45 The most often-used animal models allow investigations into the mechanisms of action at the cellular and molecular level for the purpose of studying therapeutic strategies.46,47 However, until an animal model can accommodate a range of model allergens over a wide range of sensitivities, a standardized protocol for food allergens in animals remains a challenge for use as a predictive tool.
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