CHARACTERIZATION OF A NANOPARTICLE-BASED VACCINE

RIZZO, GASTON; CHAVERO, CAMILA; BIANCHI, DAIANA; HERRERA, SANTIAGO; AGAZZI, MAXIMILIANO; CORTEZ, LORENA; MARMISOLLÉ, WALDEMAR; AZZARONI, OMAR; DOCENA GUILLERMO H; SMALDINI PAOLA L

Congreso; Reunion Annual de la Sociedad Argentina de Inmunología; 2021

Nanotechnologyplays an important role in vaccine development. It offers the opportunity todesign different functional nanoparticles based on different compositions,sizes, shapes and surface properties and for applications in biomedicine. Thiswork aimed to characterize nanoparticles as a safe vehicle and adjuvant forfurther use in immunotherapies.Polycationicnanoparticles (Np) were characterized using human and murine antigen-presenting cells (APCs). Nanoparticle-driven cell interaction was evaluated byfluorescence microscopy (internalization and localization), flow cytometry(cell activation-MHCII and CD86 expression) and ELISA (IL-1β secretion).Furthermore, Balb/c mice were intraperitoneally and intranasally administeredwith Np-OVA and the pharmacokinetic was monitored using fluorescent Np. Finally,humoral (serum antibodies) and cellular immune responses (cell subsets andcytokines) were evaluated by ELISA and flow cytometry.Wefound that Np were internalized and cells became activated, showing increasedexpression of CD86 and secretion of IL-1β. Experiments in cell lines showed thatNp promoted a higher cell stimulation with enhanced IL-1β secretion than thepositive control with an inflammasome activator (P<0.05). The IL-1βproduction was abrogated with different inflammasome inhibitors. In vivoexperiments showed that Np protected OVA through the mucosa passage, with a significantinduction of serum OVA-specific IgG, increased secretion of IFN-γ by spleencells and high frequency of LT CD4+IFN-γ+ and LT CD8+IFN-γ+ cells (p<0.05).Inconclusion, we found that APC internalized Np and activated the inflammasomepathway with IL-1β secretion. Remarkably, this nanoparticle exhibited adjuvantproperties for mucosal targeting to induce Th1-dependent immunity that could beexploited in preventive or therapeutic vaccine development for infectious andnon- infectious diseases, respectively@font-face{font-family:"Cambria Math";panose-1:2 4 5 3 5 4 6 3 2 4;mso-font-charset:0;mso-generic-font-family:roman;mso-font-pitch:variable;mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:swiss;mso-font-pitch:variable;mso-font-signature:-536859905 -1073732485 9 0 511 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0in;mso-pagination:widow-orphan;font-size:12.0pt;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;mso-no-proof:yes;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:"Calibri",sans-serif;mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:Calibri;mso-fareast-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}div.WordSection1{page:WordSection1;}