Predictive model for the sensitising capacity of novel nutritional proteins
This project will develop cell-based models to predict immunogenic and allergenic properties of (novel) proteins and derived products. These models are intended to be used in guiding the replacement of animal proteins by sustainable alternatives, e.g. legumes, cereals, algae etc., re. safety of the product for the potentially allergic or immune-sensitive individual. The proposal contributes to the mission “Circular agriculture (A)” of the joint Top Sectors Knowledge and Innovation Agenda.
The project objectives are:
- Generate a toolbox based on in vitro models that represent key events in the immunological reaction leading to allergic sensitisation;
- Generating new insights in processing effects and product matrix on bioactivity of protein allergens;
- Relation between in vitro outcomes and clinical relevancy;
- Evaluating novel protein samples on immunological activities regarding the AOP analyses.
The objective of this proposal is to develop and validate (miniaturised) in vitro tools to predict immunogenic properties of (novel) sustainable (processed) proteins. These tools can be used in food manufacturing, aiming to deliver safe products for the potentially atopic and/or immune-disbalanced individual. The development of such an assay tool set is an unmet need, as currently no predictive models exist to measure these protein characteristics. This matches with the objective of the MMIP A4 ‘Eiwitvoorziening voor humane consumptie (Protein supply for human consumption): Improvement and sustaining of the production chain for the production of proteins for human nutrition, optimally and sustainably tuning products and processes, aimed at the production of proteins of optimal quality (taste, texture, health, safety)’. The availability of such an assay tool to the food industry will contribute to the prevention of the emergence of allergies, a theme that closely matches the Dutch Science Agenda and the NFU, where prevention is a central theme as part of the ‘Sustainable Health’ research science program.
In March 2021, PREFER started with 5 industrial partners (Danone/Nutricia Research BV, Arla Foods Ingredients Group P/S, Cargill R&D Centre Europe BV, Societé des Produits Nestlé SA & Phycom) and 3 research partners (Wageningen Food & Biobased Research, Utrecht University & Erasmus MC Rotterdam). In October 2021, a two new partners have joined the consortium: The Seaweed Company BV and Mycorena AB.
The project is divided into 5 work packages (WPs). The focus of each WP is shown below. Knowledge transfer is addressed in WP 6 focussing on communication and dissemination.
- WP 1 Characterisation and processing of benchmark proteins, providing the training samples, including processing effects and their characterisation, to be tested in WP2-4.
- WP 2 Development of advanced in vitro models, providing a set of cell-based screening models mimicking the skin and intestinal epithelium including immune cell interactions, to obtain insights of a proteins’ capacity to skew the immune system to allergic sensitisation.
- WP 3 An integrated skin-gut-immune-axis-on-a-chip, in which the individual models developed in WP2 are integrated into one miniaturised chip assay in which the skin epithelium is connected to the intestinal epithelium via an immune migration axis.
- WP 4 Clinical studies, providing translational relevance through linking of the in vitro cell models to in vivo data.
- WP 5 Application to novel proteins and alternative processing techniques, evaluating the immunoreactivity of alternative processing techniques or novel proteins using the developed models in WP2-4.
Planning is done on two levels:
• An overall planning, as described in the project plan, with deliverables for the entire duration of the project.
• A detailed planning for each WP, discussed in the consortium.
In 2022, the activities in PREFER will be continued according to the overall planning described in the project plan and the detailed planning discussed with the partners for the different WPs. Special focus will be on:
• Development of the skin and intestinal epithelial in vitro models as well as setting up the measurements for the in vivo study.
Interaction between WPs: in addition to the activities belonging to individual WP, many interactions are foreseen between the WPs, e.g. by transferring fundamental results between the WPs, and by using insights from one WP in another WP.
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