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Review
. 2020 Jul 20;21(14):5130.
doi: 10.3390/ijms21145130.

Self-Amplifying RNA Viruses as RNA Vaccines

Kenneth Lundstrom  1
Affiliations
Review

Self-Amplifying RNA Viruses as RNA Vaccines

Kenneth Lundstrom. Int J Mol Sci. .

Abstract

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases.

Keywords: RNA replicons; RNA vaccines; RNA vectors; immune responses; protection against pathogens; protection against tumor challenges.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Semliki Forest virus-based expression systems. A. Schematic illustration of expression and helper vectors. Dark triangle, SP6 RNA polymerase promoter; light triangle, Semliki Forest virus (SFV) 26S subgenomic promoter. B. RNA replicon (naked RNA or liposome-encapsulated RNA), recombinant virus particles or DNA replicon (DNA plasmid) can be used for transfection/infection of cell lines and immunization of animals and humans.
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