Synthesis of a dendritic cell-targeted self-assembled polymeric nanoparticle for selective delivery of mRNA vaccines to elicit enhanced immune responses

Abstract

Recent development of SARS-CoV-2 spike mRNA vaccines to control the pandemic is a breakthrough in the field of vaccine development. mRNA vaccines are generally formulated with lipid nanoparticles (LNPs) which are composed of several lipids with specific ratios; however, they generally lack selective delivery. To develop a selective delivery method for mRNA vaccine formulation, we reported here the synthesis of polymeric nanoparticles (PNPs) composed of a guanidine copolymer containing zwitterionic groups and a dendritic cell (DC)-targeted aryl-trimannoside ligand for encapsulation and selective delivery of an mRNA to dendritic cells. A DC-targeted SARS-CoV-2 spike mRNA–PNP vaccine was shown to elicit a stronger protective immune response in mice compared to the traditional mRNA–LNP vaccine and those without the selective delivery design. It is anticipated that this technology is generally applicable to other mRNA vaccines for DC-targeted delivery with enhanced immune response.