In planta bio-encapsulation for allergen immunotherapy

Plants can be used in many ways to produce pharmaceutical proteins and offer product- specific advantages for specific applications. For example, plant-specific options for encapsulating active ingredients in storage organelles are available for administration via the mucosa of the digestive tract. These organelles are usually found in seeds, but can also be induced in leaves and their structure can be varied as synthetic organelles so that controlled release of the recombinant drug can be achieved. In the present project, this strategy will be explored and evaluated for immunotherapeutics. These will be incorporated into synthetic protein bodies consisting of multiple components and layers to achieve different levels of stability and defined release kinetics. Such a strategy is promising for improving specific immunotherapy for treating allergic diseases. Allergen- specific immunotherapy is a treatment that is well established in respiratory and insect venom allergies. However, in the treatment of food allergies, conventional subcutaneous immunotherapy is often associated with undesirable side effects, requires long treatment periods, and may not always provide lasting symptom improvement. These drawbacks can be partially overcome by the use of hypoallergenic allergen mutants and alternative routes of administration such as sublingual (SLIT) or oral (OIT) immunotherapy. However, one of the problems with mucosal delivery is that orally administered allergens are exposed to degrading enzymes and/or pass through the gastrointestinal tract where digestion of the substances occurs. Therefore, in the present project, food allergens and their hypoallergenic mutants, which represent a promising possibility for use in sublingual and/or oral immunotherapy, will be incorporated into multilayered plant storage organelles, which is expected to result in higher stability and thus improved efficacy. This assumption will be investigated by a comprehensive molecular and cell biological analysis and by using a murine food allergy model.