Rise of the RNA machines - self-amplification in mRNA vaccine design

Jerome D G Comes; Gorben P Pijlman; Tessy A H Hick

doi:10.1016/j.tibtech.2023.05.007

Rise of the RNA machines - self-amplification in mRNA vaccine design

Trends Biotechnol. 2023 Nov;41(11):1417-1429. doi: 10.1016/j.tibtech.2023.05.007. Epub 2023 Jun 14.

Authors

Jerome D G Comes¹, Gorben P Pijlman², Tessy A H Hick¹

Affiliations

¹ Wageningen University and Research, Laboratory of Virology, Droevendaalsesteeg 1, 6708PB, Wageningen, The Netherlands.
² Wageningen University and Research, Laboratory of Virology, Droevendaalsesteeg 1, 6708PB, Wageningen, The Netherlands. Electronic address: gorben.pijlman@wur.nl.

Abstract

mRNA vaccines have won the race for early COVID-19 vaccine approval, yet improvements are necessary to retain this leading role in combating infectious diseases. A next generation of self-amplifying mRNAs, also known as replicons, form an ideal vaccine platform. Replicons induce potent humoral and cellular responses with few adverse effects upon a minimal, single-dose immunization. Delivery of replicons is achieved with virus-like replicon particles (VRPs), or in nonviral vehicles such as liposomes or lipid nanoparticles. Here, we discuss innovative advances, including multivalent, mucosal, and therapeutic replicon vaccines, and highlight novelties in replicon design. As soon as essential safety evaluations have been resolved, this promising vaccine concept can transform into a widely applied clinical platform technology taking center stage in pandemic preparedness.

Keywords: lipid nanoparticles; mRNA; platform technology; replicon; self-amplifying RNA; vaccines.

Publication types

Review