Use of a polymeric nanoparticle as an adjuvant to actívate mucosal and systemic innate and adaptative immunity

RIZZO, GASTON; ELIZAGARAY, MAIA; CHAVERO, CAMILA; BIANCHI, DAIANA; APUZZO, EUGENIA; HERRERA, SANTIAGO; AGAZZI, MAXIMILIANO; MORENO, GRISELDA; AZZARONI, OMAR; DOCENA GUILLERMO H; PAOLA L. SMALDINI

Congreso; SAIC ? SAI-FAIC- SAFIS; 2022

Nanotechnology plays an important role in vaccine development. It offers theopportunity to design different functional nanoparticles (Np) based on differentcomposition, size, shape and surface properties for biomedical applications. This workaimed to characterize Np as a safe vehicle and adjuvant to be further used in vaccines.Nanoparticles were characterized using human and murine antigen-presenting cells(APCs) and epithelial cells. Cell interaction was evaluated by fluorescence microscopy(internalization and localization), flow cytometry (activation-MHCII and CD86expression) and ELISA (IL-1β secretion). Furthermore, Balb/c mice wereintraperitoneally and intranasally administered with Np-OVA and the pharmacokineticwas monitored using Np-FITC. Finally, humoral and cellular immune responses (cellsubsets and cytokines), and lung-resident memory T cells (Trm) were evaluated byELISA and flow cytometry.We found that Np were internalized only by APC and cells became activated, showinga significant increased expression of CD86 and activation of the inflammasome withsecretion of IL-1β. The IL-1β production was abrogated with different inflammasomeinhibitors. In vivo experiments showed that Np protected OVA through the mucosapassage, and Np-OVA reached the critical organs to promote immune activation. Weobserved a significant induction of serum OVA-specific IgG, increased secretion of IFN-γ by splenocytes with a high frequency of CD8+- and CD4+-IFN-γ+secreting cells.Remarkably, lung CD62L-CD69+ Trm cells (p<0.05) and mucosal IgA were induced.In conclusion, we found that APC internalized Np and activated the inflammasomepathway promoting IL-1β secretion and B and T cells induction. Remarkably, thisnanoparticle exhibited adjuvant properties for mucosal targeting to induce Th1-dependent immunity and Trm cells that could be exploited in preventive or therapeuticvaccine development for infectious and non-infectious diseases, respectively.