Microparticles for oral immunotherapy of type I food allergy

Even though hyposensitization represents to date the only accepted causative treatment of type I allergy, it is not recommended for food allergy therapy due to the frequency and severity of possible side effects. Thus, strict avoidance of the offending food is the only accepted treatment option for food allergic patients. This project aims to develop a safe treatment for food allergy applied via the oral route. It is crucial to prevent possible side effects of the oral vaccine by 1.) targeting specifically the immune induction sites of the gastrointestinal tract, 2.) avoiding triggering of sensitized cells and 3.) allowing long-term memory. In order to optimize stimulation of the immune system, the orally applied allergen has to be protected against gastrointestinal degradation by a carrier material to ensure maximal antigen accumulation at Peyers patches of the intestinal mucosa. Previously, we have demonstrated in mouse experiments that encapsulation of allergens in biocompatible poly(D,L-lactic-co-glycolic acid) (PLGA) particles may represent a promising candidate as novel oral vaccine. Encapsulating allergens into microparticles ensures a rather slow release of the allergen, thus, guaranteeing patient`s safety. Furthermore, the particles` surface can be functionalized with bioactive substances (in this project a functionalization with Aleuria Aurantia lectin (AAL) or Neuraminidase (NA) from Vibrio cholerae is intended) in order to bind specifically above the gut- associated lymphoid tissue (GALT), the M-cells, for improving efficacy. Preliminary data of a murine model showed that functionalization of allergen-loaded PLGA particles with AAL and NA modulates an ongoing grasspollen allergy by the reduction of allergen-specific IgE and induction of specific IgA antibodies and immunomodulatory cytokines IL10 and TGF-beta. Based on these data, we expect to characterize allergen-loaded microparticles as an efficient and safe treatment option for food allergy in this project.