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Review
. 2012 Nov;9(11):1319-30.
doi: 10.4161/rna.22269. Epub 2012 Oct 12.

Developing mRNA-vaccine technologies

Affiliations
Review

Developing mRNA-vaccine technologies

Thomas Schlake et al. RNA Biol. 2012 Nov.

Abstract

mRNA vaccines combine desirable immunological properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addition, mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the production process, mRNA vaccines also offer maximum flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technology platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technology.

Keywords: adjuvant; formulation; mRNA; mRNA design; mRNA production; mRNA uptake; protein expression; vaccine.

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Figures

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Figure 1. Protein expression in vivo is strongly prolonged using CureVac’s proprietary mRNA technology and lasts for many days. Firefly luciferase-encoding mRNA, optimized for translation and stability, was injected intradermally in a BALB/c mouse (4 injection sites). At various time points after mRNA injection, luciferase expression was visualized in the living animal by optical imaging. (A) Visualization of luciferase expression at selected time points, showing maximal protein levels 24 to 48 h after mRNA injection. (B) Time course of luciferase expression until 9 d after mRNA injection. Background signal was set to 1.
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Figure 2. A biologically relevant increase of reticulocytes is induced in mice using CureVac’s proprietary mRNA technology. A single intramuscular injection in BALB/c mice of erythropoietin (Epo)-encoding mRNA, optimized for translation and stability, causes the expression of functional Epo. Reticulocyte levels are raised comparably by mRNA and recombinant protein injected intramuscularly.
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Figure 3. CD40 ligand as an accessory adjuvant molecule encoded by mRNA increases the anti-tumor effect of a two-component mRNA vaccine. Mice (n = 8 per group) were challenged subcutaneously with syngenic E.G7-OVA tumor cells on day 0. Commencing on day 7, mice were vaccinated intradermally with either OVA-mRNA vaccine alone or in combination with mRNA coding for CD40 ligand according to the indicated schedule. Mice treated with buffer served as the control. The combination of CD40 ligand-encoding mRNA together with OVA mRNA vaccination increases the efficacy of the therapeutic anti-tumor mRNA vaccination.

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