Messenger RNA (mRNA) vaccines have exhibited promising potential for infectious disease prevention. Although various delivery methods have been explored, the use of electroporation (EP) for the delivery of naked mRNA has received relatively less attention. In this study, we used mouse models to investigate whether naked mRNA vaccine delivery via intramuscular EP (IM-EP) elicits a protective immune response against lethal viral infection. To achieve this, we injected C57BL/6 mice with naked mRNA encoding the SARS-CoV-2 mRNA vaccine via IM-EP and evaluated the resulting immune responses. IM-EP-mediated delivery of the mRNA vaccine induced robust humoral and cellular immune responses, characterized by elevated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibodies, enhanced IFN-γ production by CD8⁺ T cells, and upregulated cytokine expression in the muscle and lymph nodes. Using the K18-hACE2 mouse model, we revealed that IM-EP-mediated delivery of the naked mRNA vaccine effectively protected mice from lethal SARS-CoV-2 infection. Overall, our findings suggest that the delivery of naked mRNA via IM-EP can be an effective strategy for preventing infectious diseases.

Journal of Biomedical and Translational Research