Abstract
Successful DNA vaccination generally requires the aid of either a viral vector within vaccine components or electroporation device into muscle or skin of the host. However, these systems come with certain obstacles, including limited transgene capacity, broad pre-existing 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), named PLA-PEG, as surface engineering agent that conciliates lipid nanoparticle (LNP) between stability during preparation and biocompatibility post-vaccination. The LNP carrier can be loaded with 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.
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