Gantrez an nanopartilces for allergen immunotherapy

Résumé

Allergen-specific immunotherapy (SIT) involves repeated administrations of the sensitizing allergen and it has been shown to be a robust and clinicali y effective approach, improving the quality of life of the treated individuals, through the reduction of symptoms and medication usage. However, it implies certain drawbacks which could be minimized by the use of good adjuvants, capable of amplifying the appropriate immune response with minimal adverse effects. in this context, the adjuvant capacity of Gantrez® AN nanoparticles with ovalbumin (OVA) as model allergen was studied. The influence of the immune response of the OVA location (coatinq the surface or encapsulated into the matrix) as well as the effect of cross-linkage of nanoparticles on the antibody immune response was also evaluated. Furthermore, some batches were also loaded with lipopolysaccharide of Brucella ovis to study its immunomodulator effect. Once the formulations were optimized, their protective effect with or without LPS was evaluated on a model of OVA-sensitized mi ce. The mi ce were treated with the OVA-entrapped nanoparticles with or without LPS by both intradermal and oral route and finally were challenged and the different anaphylactic symptoms were observed. By intradermal route, OVA-entrapped nanoparticles with encapsulated LPS protected all the mi ce from death while the control group immunized with OVA-Alum showed 80% of mortality. In this case, the lipopolysaccharide of Brucella ovis seemed to improve the adjuvant characteristics of the nanoparticles.%&/on the otner hand, by oral route, OVA-entrapped nanoparticles protected all the mi ce from death, being more efficient this formulation than the one with encapsulated LPS. This fact could be related to the hyporesponsiveness of the gastrointestinal tract against the LPS. in the final part of this work, nanoparticles with encapsulated Lolium perenne extract were prepared and administered to pre-sensitized mice to Lolium. The results obtained in this thesis are very encouraging for future use of Gantrez® AN nanoparticles as adjuvant for immunotherapy.