Mechanism of action of mRNA-based vaccines

ABSTRACT

Introduction: The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines.

Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems.

Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine.

KEYWORDS:

• Intrinsic adjuvanticity
• innate immunity
• antiviral response
• type I interferon
• delivery system
• optimization
• self-amplifying mRNA (SAM)

Acknowledgments

Part of the work reported on SAM was supported by DARPA, Defense Advanced Research Project Agency under agreement HR0011-12-3-001. All authors were involved in drafting the manuscript or revising it critically for important intellectual content. The authors thank Ulrike Krause for excellent technical assistance and Giulietta Maruggi for helpful discussions during the critical review of the manuscript.

Declaration of interest

All authors are employees of the GSK group of companies. N Delahaye reports owning restricted shares in the GSK group of companies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The manuscript was funded by GlaxoSmithKline Biologicals SA.