Bacterial Membrane Coating Potentiates Lipid Nanoparticles for mRNA Delivery

Bacterial outer membrane vesicles (OMVs) possess intrinsic immunostimulatory properties by carrying native antigens and pathogen-associated molecular patterns (PAMPs). Lipid nanoparticles (LNPs) have become the leading platform for messenger ribonucleic acid (mRNA) delivery, underpinning the clinical success of mRNA vaccines. Here, we developed a hybrid nanoparticle formulation, OMV-coated LNPs (OMV-LNPs), that combines the high delivery efficiency of LNPs with the immunogenicity of the OMVs to enhance gene delivery. Using Escherichia coli-derived OMVs and dengue virus (DENV) E80 protein as a model antigen, we generated OMV-LNPs encapsulating DENV mRNA (OMV-LNP_mRNA). These nanoparticles demonstrated improved uptake by lymph-node-resident immune cells and enhanced cytosolic mRNA delivery, resulting in robust dendritic cell maturation and proinflammatory cytokine production in vitro. In AG129 mice, the OMV-LNP_mRNA elicited significantly higher titers of DENV-neutralizing antibodies compared to conventional LNPs. Collectively, these results establish OMV-LNPs as a versatile and potent platform for effective mRNA vaccine delivery.