Advancements in molecular and translational allergology Safety and immunogenicity of chemically modified peanut allergens and nanoparticle-based delivery systems

In 1911, the first evidence of successful, disease modifying, allergen-specific immunotherapy (AIT) was published. Currently, there is still a lot of room for improving AIT to make this treatment the first choice for allergologists. Because of the high risk of allergic side-effects, the first aim of this thesis was to explore a safe AIT concept for peanut allergy. The second aim was to explore the possibility of using nanoparticles as an alternative for the widely used but increasingly scrutinized adjuvant alum in AIT. For a safe AIT concept for peanut allergy, we chemically modified a peanut extract to reduce its allergenicity (hypoallergenicity) and established a pre-clinical proof of concept of the modified peanut extract in mouse models. Also, we found that the safety could be further enhanced by adsorbing the peanut allergens to alum. During our investigation we also found that, Ara h 2, a major peanut allergen, appeared linked to another major peanut allergen, Ara h 1, which offers an alternative explanation for the earlier reported cross-reactivity between these two allergens.
For the second aim we designed two novel AIT concepts based on Bet v 1, the major birch pollen allergen. The first concept consisted of Bet v 1 bound to the surface of liposomes via a novel linkage system. The second concept consisted of elastin-like polypeptide (ELP) nanoparticles Both concepts showed promising hypoallergenicity which is important for safety but also showed different immunogenicity profiles. Nevertheless, both nanoparticle-based concepts are promising alternatives for alum in AIT.