The Shape of Nanostructures Encodes Immunomodulation of Carbohydrate Antigen and Vaccine Development

Gold nanoparticles (AuNPs) have shown remarkable potential for vaccine development, but the influence of the size and shape of nanoparticles modulating the T-cell-dependent carbohydrate antigen processing and immunomodulation is poorly investigated. Here, we described how different shapes and sizes of gold nanostructures carrying adjuvant modulate carbohydrate-based antigen processing in murine dendritic cells (mDCs) and subsequent T-cell activation produce a robust antibody response. As a prototype, CpG-adjuvant-coated spherical and rod- and star-shaped AuNPs were conjugated to the tripodal Tn-glycopeptide antigen to study their DC uptake and activation of T-cells in a DCs/T-cell co-culture assay. Our results showed that the spherical and star-shaped AuNPs displayed relatively weak receptor-mediated uptake and endosomal sequestration; however, they induced a high level of T helper-1 (Th1) biasing immune responses compared with rod-shaped AuNPs. Furthermore, the in vivo administration of AuNPs showed that the small spherical and star-shaped AuNPs induced an effective anti-Tn-glycopeptide immunoglobulin (IgG) antibody response compared with rod-shaped AuNPs. These results indicated that one could obtain superior carbohydrate vaccines by varying the shape and size parameters of nanostructures.