Three decades of messenger RNA vaccine development Author links open overlay panelReinVerbekeabIneLentackerabStefaan C.De Smedtab1HeleenDewitteabc1 https://doi.org/10.1016/j.nantod.2019.100766Get rights and content Highlights • mRNA represents an attractive source of antigen in vaccination approaches.
• Both unformulated and nanoparticulate mRNA are used for direct in vivo vaccination.
• Nanoformulation widens the administration and delivery options for mRNA vaccines.
• The self-adjuvant effect of mRNA is a double-edged sword for vaccine efficacy.
• Rationale for combining mRNA cancer vaccines with checkpoint inhibition.
Abstract In the early nineties, pioneering steps were taken in the use of mRNA as a therapeutic tool for vaccination. In the following decades, an improved understanding of the mRNA pharmacology, together with novel insights in immunology have positioned mRNA-based technologies as next-generation vaccines. This review outlines the history and current state-of-the-art in mRNA vaccination, while presenting an immunological view on mRNA vaccine development. As such, we highlight the challenges in vaccine design, testing and administration, key considerations in the design of mRNA-based vaccines and new opportunities that arise when packaging mRNA in nanoparticulate vaccines. Finally, we discuss the mRNA self-adjuvant effect as a critical, but dichotomous parameter that determines the safety, efficacy and strength of the evoked immune response.
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