Use of mRNA for vaccination or gene therapy: delivery route determines the verdict (P4316)

Abstract

Abstract The use of DNA and viral vector vaccines for the induction of cellular immune responses is increasingly gaining interest. However, concerns have been raised regarding the safety of these immunization strategies. Due to their lack of genome integration, mRNA-based vaccines have emerged as a promising alternative. In this study we evaluated the potency of antigen-encoding mRNA either delivered via complexation with the cationic lipid DOTAP/DOPE, or delivered via in vivo electroporation as a novel vaccination approach. By using luciferase-encoding mRNA we showed that in vivo electroporation of mRNA induces high levels of luciferase at the injection site, while protein expression in mice injected with DOTAP/DOPE complexed mRNA was barely above background levels. Despite the high levels of protein expression, in vivo electroporation of mRNA failed to elicit immune responses against the encoded antigen. In contrast, lipid-based delivery of mRNA induced antigen-specific, functional T cell responses resulting in specific killing of peptide-pulsed cells and the induction of humoral responses. In summary, in vivo electroporation of antigen-encoding mRNA induces high levels of protein expression but no immune responses, thus presenting an ideal tool for mRNA-based gene therapy, while lipid-based delivery offers advantages for vaccination purposes due to the induction of low protein levels but strong antigen-specific cellular immunity.