Plant-based production and bioencapsulation of immunotherapeutics for allergy treatment

Background.

Plants are versatile production and delivery vehicles for recombinant protein pharmaceuticals. For mucosal application strategies, plants also allow the bioencapsulation of proteins within the plant matrix and even within intracellular organelles, such as the protein storage organelles commonly found in seeds. It is also possible to induce the ectopic formation of storage organelles (known as protein bodies) in leaf tissues, where they are not usually found. This is a promising strategy for the improvement of immunotherapy for allergies. Allergen-specific immunotherapy is a disease-modifying treatment already established for respiratory and insect venom allergies. However, traditional subcutaneous immunotherapy is not recommended for the treatment of food allergies due to frequent adverse side effects, long treatment periods, and only transient improvement of symptoms. These drawbacks have been addressed by the use of hypoallergenic allergen mutants and different administration routes including mucosal interventions such as sublingual and oral immunotherapy. The latter has been tested for the treatment of several food allergies, with promising clinical and immunological outcomes. However, orally administered allergens must pass through the gastrointestinal tract, where they are exposed to proteolytic digestion. For example, the hypoallergenic version of parvalbumin is a promising therapeutic candidate for the treatment of fish allergies, but is unstable following mucosal delivery and therefore unable to induce oral tolerance.

Aims and methods.

We hypothesize that plants are suitable as production and delivery vehicles for parvalbumin and that in planta bioencapsulation will help to protect the allergens from degradation. We will design, purify and characterize parvalbumin-containing multi-component protein bodies with a core-shell structure featuring different stability and release kinetics. We will evaluate the stability of these protein bodies, their uptake into antigen-presenting cells, and their efficacy in a murine allergy model. The project will provide further insight into protein storage organelle formation and synthetic approaches to produce customized, therapeutic protein storage organelles directly in the plant production host. The novel bioencapsulation strategies established in the project will also be applicable to a wide variety of immunotherapeutics and other protein pharmaceuticals for mucosal delivery.

Collaborations.

The project is a collaborative effort bringing together the research groups of Prof Eva Stoger (University of Natural Resources and Life Sciences), Prof Ines Swoboda (FH Campus Vienna) and Prof Eva Untersmayr-Elsenhuber (Medical University of Vienna) with complementary backgrounds in plant biotechnology, immunology and allergology, respectively.

Freidl R et al. (2019) Resistance of parvalbumin to gastrointestinal digestion is required for profound and long-lasting prophylactic oral tolerance Allergy doi:10.1111/all.13994
Hofbauer A et al. (2016) The Encapsulation of Hemagglutinin in Protein Bodies Achieves a Stronger Immune Response in Mice than the Soluble Antigen Front Plant Sci 7:142 doi:10.3389/fpls.2016.00142
Schwestka J et al. (2020) Plant-derived protein bodies as delivery vehicles for recombinant proteins into mammalian cells Biotechnol Bioeng 117:1037-1047 doi:10.1002/bit.27273