Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Abstract

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory‐to‐laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma

“…In food allergy, the focus is on genetic risk factors, allergen-specific and nonspecific humoral and cellular biomarkers. [158][159][160] Although genetic markers for food allergy are not yet at the level of clinical relevance, genes linked to HLA-genes, and more importantly to epithelial integrity and consequently reduced barrier function like filaggrin, SPINK5 161 and SERPINB7, are linked to eczema development and also food allergy. [162][163][164][165][166][167][168] Given the importance of Although allergen-specific T-cells are extremely rare, they display a pronounced Th2 type in allergic individuals.…”

“…Apart from clinical determinants of food allergy and the respective gold standard, the oral food challenge, biomarkers represent an area of extensive research. In food allergy, the focus is on genetic risk factors, allergen‐specific and nonspecific humoral and cellular biomarkers 158–160 …”

Recent developments and highlights in food allergy

“…The mechanisms underlying food allergy are complex, are multidimensional, and are often heavily influenced by environmental factors that sometimes require experimentation in animal models. 79,80 In addition, animal models can be useful in elucidating the mechanisms connecting allergic responses at different body sites (eg, lung-gut or skin-gut axis). Recently, it was shown in mice that epicutaneous immunotherapy can protect against food-induced anaphylaxis.…”

Production of allergen-specific immunotherapeutic agents for the treatment of food allergy

“…This can involve several in vitro and ex vivo methods, including IgE binding assays using ELISA or Western blot, IgE cross-linking in basophil or mast cell assays, and T cell proliferation and cytokine assays, which in addition to in silico method are common in the evaluation of protein allergenicity [163]. A similar array of methods can be used for mechanism of action studies of IT agents in animal models [43,164,165], and during clinical trials [6,166].…”