PPS PREFER: Model to predict allergic sensitisation capacity of novel nutritional proteins

The demand for (novel) proteins from sustainable sources, such as plants and waste-streams, is growing, and it is vital that these new ingredients conquer a permanent place in the human diet. However, despite having GRAS (Generally Recognized as Safe)-status, they could cause allergic sensitisation in consumers. Sensitisation - the first stage of developing an allergy - is the moment that the immune system recognizes a (novel) protein as potentially harmful. Manufacturers who are using novel proteins in their products, are obligated to investigate whether these proteins could cause sensitisation, before introducing them to the market.

Allergic sensitisation risk assessment

The European Association for Allergy and Clinical Immunology (EAACI) forecasts that in 2025 more than 50% of all Europeans will suffer from at least one type of allergy while, simultaneously, novel proteins with potential allergic risks will be introduced in our diets. To predict whether a (novel) protein can provoke an allergic reaction, the trigger of the allergic reaction cascade needs to be identified and its down-stream effects evaluated. To reliably investigate this sensitisation stage, a robust model is needed. However, suitable animal models to predict allergic sensitisation are not available. The relevance of these specific animal models to humans can be disputed, and there is a strongly growing societal demand to stop animal experimentation. Hence alternative measurement methods need to be developed.

Predicting allergenic sensitisation potential

In the PREFER project a toolbox will be generated and optimized to predict the allergenic sensitisation potential of a protein. This will be done based on in vitro models, including Organ-on-a-Chip models, that represent key events in the immunological response. Think of cell cultures that represent the intestinal and the skin epithelium, including different types of immune cells (dendritic cells, T-cells and B-cells). The toolbox will be subsequently validated with human data.

The outcome will be predictive in vitro models that enable food industries to test their proteins and food products, in order to:

1. Develop processing technologies aimed at influencing proteins to adversely or beneficially interact with the immune response
2. Support product registration at regulatory agencies such as the European Food Ssafety Authority (EFSA) for, e.g., novel food dossiers

Five research lines

The project has 5 main research lines:

1. Selection and processing of proteins
2. Development of advanced in vitro models
3. An integrated skin-gut-immune-axis on-a-chip
4. Clinical studies and translational validation through linking in vitro and in vivo models
5. Application of the model to novel protein (products)

From protein types to processing conditions

Partners contributing (novel) protein sources will gain immediate knowledge about the immunogenicity and sensitizing properties of their product, via in vitro and Organ-on-a-Chip model systems. End users will gain information about protein types, processing conditions (such as heating and its impact on protein structure, e.g. glycation or unfolding), matrix components (such as carbohydrates and lipids) that could be applicable to commercial products. The project (outcomes) will open up opportunities to tune products, production and formulations to develop new nutritional solutions – crucial for success in the rapidly changing global protein market.