Bioinspired vaccines to enhance MHC class-I antigen cross-presentation

Cross-presentation of exogenous antigen on MHC class-I is a crucial process for generating a CD8⁺ T cell response, and is therefore an important design consideration in the development of T-cell-engaging vaccines against viruses, intracellular bacteria, and cancers. Here, we briefly summarize known cross-presentation pathways and highlight how synthetic vaccines can be engineered to enhance MHC-I presentation of exogenous peptide and protein antigens by professional antigen-presenting cells (APCs). In particular, we summarize how molecular engineering and nanotechnology are being harnessed to enhance antigen delivery to lymph nodes and to cross-presenting dendritic cells, to bypass endosomal trafficking of exogenous antigen to promote delivery of antigen to the cytosol of APCs, and to coordinate the delivery of antigen with immune-stimulating adjuvants that can act synergistically to augment antigen cross-presentation.