Boosting DNA vaccine power by lipid nanoparticles surface engineered with amphiphilic bioresorbable copolymer

Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or an electroporation device into the muscle or skin of the host. However, these systems come with certain obstacles, including limited transgene capacity, broad preexisting immunity in humans, and substantial cell death caused by high voltage pulses, respectively. In this study, we repurposed the use of an amphiphilic bioresorbable copolymer (ABC), called PLA-PEG, as a surface engineering agent that conciliates lipid nanoparticles (LNPs) between stability during preparation and biocompatibility post-vaccination. The LNP carrier can be loaded with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-specific DNA; in this form, the DNA-LNP is immunogenic in hamsters and elicits protective immunity following DNA-LNP vaccination against heterologous virus challenge or as a hybrid-type vaccine booster against SARS-CoV-2 variants. The data provide comprehensive information on the relationships between LNP composition, manufacturing process, and vaccine efficacy. The outcomes of this study offer new insights into designing next-generation LNP formulations and pave the way for boosting vaccine power to combat existing and possible emerging infectious diseases/pathogens.