Adjuvant dendritic mesoporous silica nanoparticles as sustained delivery system for peptide-based vaccine

Peptide-based vaccines have raised as an attractive alternative strategy to overcome many of the limitations of conventional vaccines. Some drawbacks for an optimal immune response in vivo are, a poor immunogenicity, multivalency, a requirement of adjuvants and a delivery system. The peptide vaccine B2T confers full protection in swine against foot-and-mouth disease virus. Besides the clinical need to design more efficient delivery systems, there is a market need due to the economic losses associated with this disease worldwide. To overcome these challenges, I have exploited mesoporous silica nanoparticles. These nanoparticles have been extensively studied for vaccine delivery and some reports indicate self-adjuvant properties. Within this PhD, I have synthesized and characterized dendritic mesoporous silica nanoparticles (DMSNs), a type of mesoporous silica nanoparticle. The DMSNs have excellent colloidal stability and have a size of 57 nm and 156 nm. I have efficiently loaded B2T into DMSNs (B2T@DMSNs) (570~580 µg/mg). I demonstrated a sustained and prolonged release of the peptide over time (930 h). The B2T@DMSNs administered in vivo in a murine model generate strong immune response based on the high production of immunoglobulins G (IgG), dependent on the size of the DMSNs without the use of adjuvants. B2T@DMSNs elicited specific immune responses in mice with high IgG production like the reference formulation (i.e., B2T emulsified in Montanide), self-adjuvant properties of the DMSNs could be ascribed. Furthermore, at the time measured only 61% of the peptide vaccine was released from the B2T@DMSNs, thus indicating a longer sustained release compared to the B2T@Montanide. Our results display DMSNs as optimized/efficacious nanocarriers for peptide-based vaccine administration. Las vacunas basadas en péptidos se han posicionado como una estrategia atractiva para superar diversas limitaciones de las vacunas tradicionales. Sin embargo, éstas son poco inmunogénicas y requieren de una acción multivalente, de la coadministración de adyuvantes y del uso de sistemas de liberación, para una óptima respuesta inmune in vivo. La vacuna peptídica B2T confiere protección completa en porcino, contra el virus de la enfermedad de pies y boca. A parte de la necesidad clínica de diseñar y obtener sistemas de liberación más eficientes, existe una necesidad del mercado asociada a las pérdidas económicas causadas mundialmente por esta enfermedad. Para superar estos desafíos, h