Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins

Abstract

A B S T R A C TThe development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity.In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks.

Homologous tropomyosins from vertebrate and invertebrate: Recombinant calibrator proteins in functional biological assays for tropomyosin allergenicity assessment of novel animal foods

“…Prominent examples of novel foods from animal origin are edible insects or exotic meats (eg crocodile or kangaroo meat) and from plant origin, algae‐related food (eg spirulina) or novel seeds (eg chia seeds) . In the absence of studies on epidemiology and natural history of allergic reactions to novel foods, these foods bear possible risk for food‐allergic reactions in allergic patients due to clinical cross‐reactions as well as in previously tolerant individuals due to de novo sensitization . However, there is no generally accepted strategy for the allergenicity assessment of novel foods prior to market launch …”

“…By contrast, there is no generally accepted strategy of how to perform allergenicity assessment of novel foods . Recently, an European food allergy expert consortium (COST action FA1402, ImPARAS, 2014‐2018) identified important gaps in the safety assessment of novel foods with major weaknesses in guidance on allergenicity and immunogenicity assessment of food sources . A multidisciplinary strategy has been identified for future systematic and comprehensive food risk assessment, with emphasis on using well‐characterized pairs of homologous proteins as opponents on an allergenicity scale, in order to validate applied methodologies and to calibrate the assays for those cases where the putative novel food allergen is known to have allergenic/non‐allergenic homologues .…”

Statement complementing the EFSA Scientific Opinion on application (EFSA‐GMO‐UK‐2006‐34) for authorisation of food and feed containing, consisting of and produced from genetically modified maize 3272

“…The GMO Panel and the scientific community at large acknowledge the difficulty in identifying adequate in vitro or in vivo methods for the assessment of the allergenic potential of proteins, in particular those investigating de novo sensitisation risk (FAO/WHO, 2001;EFSA GMO Panel, 2010bLadics et al, 2014;EFSA, 2018Remington et al, 2018Houben et al, 2019). The GMO Panel is aware of the fact that for allergenicity assessment in vitro cell-based assays or in vivo tests on animal (2009) establishes the principles for the allergenicity assessment highlighting that if additional in vitro and/or in vivo methods are necessary, they should be scientifically sound.…”

Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

“…This can be achieved via different ways, e.g. through development of new nutritional/protein sources, improvement of crops, by providing solutions to technical challenges during manufacturing, as well as by valorizing unused side products (Remington et al, 2018;Selb et al, 2017). These foods must not pose a risk to public health, thus a comprehensive risk assessment should be conducted in order to ensure their safety.…”