Synthesis and Assembly of mRNA-Bifunctional Lipid Nanoparticle (BLNP) for Selective Delivery of mRNA Vaccines to Dendritic Cells

Abstract

ABSTRACTThe fight against COVID-19 pandemic has gained a strong consensus about the importance of developing mRNA vaccines to rapidly respond to an outbreak. Several studies have shown that mRNA vaccines formulated as mRNA-lipid nanoparticles (LNPs) for vaccination can elicit a robust and efficient immune response. In this study, we report the preparation of mRNA-bifunctional lipid nanoparticles (mRNA-BLNPs) as vaccines for targeted delivery to dendritic cells (DCs) to improve safety and enhance immune response. Using this DC-targeted delivery system, mice immunized with SARS-CoV-2 spike mRNA-BLNP vaccine elicited a stronger immune response with higher titer of neutralizing IgG antibody response than the LNPformulated vaccine against SARS-CoV-2. In addition, the spike mRNA-BLNP vaccine with deletion of glycosites in the stem elicited a broadly protective immune response against SARS-CoV2 and variants. These findings suggest the importance and potential of developing DC-targeted mRNA vaccines to elicit broadly protective immune responses against human viruses.