Synthesis of Dendritic Cell-Targeted Polymeric Nanoparticles 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 simpler method selective delivery of mRNA, we reported here the synthesis of biodegradable copolymers decorated with guanidine and zwitterionic groups and an aryltrimannoside ligand as polymeric nanoparticles (PNPs) for encapsulation and selective delivery of an mRNA to dendritic cells (DCs). A representative DC-targeted SARS-CoV-2 spike mRNA-PNP vaccine was shown to elicit a stronger protective immune response in mice as compared to the mRNA-LNP and mRNA-PNP vaccines without the selective delivery design. It is anticipated that this technology will be generally applicable to development of DC-targeted mRNA vaccines with enhanced immune response. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/566827v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@df68faorg.highwire.dtl.DTLVardef@1651a76org.highwire.dtl.DTLVardef@ac5b8borg.highwire.dtl.DTLVardef@1ae1475_HPS_FORMAT_FIGEXP M_FIG C_FIG Dendritic cell-targeted mRNA-PNP vaccines