Tu174 - Characterization of a Poly (allylamine Hydrochloride) Nanoparticle-based Adjuvant That Provides a Rapid and Broad Mucosal Immune Activation

Gaston Rizzo – Institute of Immunological and Pathophysiological Studies (IIFP-UNLP-CONICET) ARGENTINA; Rodrigo Sanchez – Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, (ICB-UFMG) BRAZIL; Camila Chavero – Institute of Immunological and Pathophysiological Studies (IIFP-UNLP-CONICET) ARGENTINA; Daiana Bianchi – Institute of Immunological and Pathophysiological Studies (IIFP-UNLP-CONICET) ARGENTINA; Evangelina Dupuy – Institute of Immunological and Pathophysiological Studies (IIFP-UNLP-CONICET) ARGENTINA; Eugenia Apuzzo – Institute of Theoretical and Applied Physicochemistry (INIFTA-UNLP-CONICET) ARGENTINA; santiago Herrera – Institute of Theoretical and Applied Physicochemistry (INIFTA-UNLP-CONICET) ARGENTINA; Maximiliano Agazzi – Institute of Theoretical and Applied Physicochemistry (INIFTA-UNLP-CONICET) ARGENTINA; Omar Azzaroni – Institute of Theoretical and Applied Physicochemistry (INIFTA-UNLP-CONICET) ARGENTINA; sergio Costa Oliveira – Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, (ICB-UFMG) BRAZIL; Smaldini Paola – Institute of Immunological and Pathophysiological Studies (IIFP-UNLP-CONICET) ARGENTINA

Abstract Text: Different functional nanoparticles (Np) can be designed based on different compositions, sizes, shape and surface properties for biomedical applications. This work aimed to characterize poly(allylamine) Np as a vehicle and adjuvant to be further used in vaccines.
Self-assembly Np were characterized using several antigen-presenting cells (APCs), epithelial cells and mice. Cell interaction and activation was evaluated by fluorescence microscopy, flow cytometry and ELISA. Finally, Balb/c mice were systemically or mucosally immunized with Np-OVA and the pharmacokinetic and immunogenicity were evaluated.
We found that APC internalized Np, which became activated, with a significantly increased expression of CD86 (p < 0.05) and IL-1β (p < 0.01). Using KO mice we demonstrated an NLRP3- and Caspase 1-dependent secretion of IL-1β. In vivo tracking experiments showed that native Np native protected OVA and reached the critical organs to promote immune activation. Then, a significant induction of serum OVA-specific IgG and IgG2a, increased secretion of IFN-γ by spleen cells and a high frequency of LT CD4+IFN-γ+ and LT CD8+IFN-γ+ cells were seen.
In conclusion, we found that APC internalized Np and activated the inflammasome pathway with IL-1β secretion. Remarkably, this nanoparticle exhibited adjuvant properties for mucosal targeting to induce a Th1-dependent immunity that could be exploited in a vaccine.