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Self-amplifying RNA vaccines for infectious diseases

Gene Therapy volume 28, pages 117–129 (2021) Cite this article

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Abstract

Vaccinology is shifting toward synthetic RNA platforms which allow for rapid, scalable, and cell-free manufacturing of prophylactic and therapeutic vaccines. The simple development pipeline is based on in vitro transcription of antigen-encoding sequences or immunotherapies as synthetic RNA transcripts, which are then formulated for delivery. This approach may enable a quicker response to emerging disease outbreaks, as is evident from the swift pursuit of RNA vaccine candidates for the global SARS-CoV-2 pandemic. Both conventional and self-amplifying RNAs have shown protective immunization in preclinical studies against multiple infectious diseases including influenza, RSV, Rabies, Ebola, and HIV-1. Self-amplifying RNAs have shown enhanced antigen expression at lower doses compared to conventional mRNA, suggesting this technology may improve immunization. This review will explore how self-amplifying RNAs are emerging as important vaccine candidates for infectious diseases, the advantages of synthetic manufacturing approaches, and their potential for preventing and treating chronic infections.

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Fig. 1: Conventional, self-amplifying, and trans-amplifying RNA vaccine designs.
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Acknowledgements

The authors gratefully acknowledge funding from the South African Medial Research Council, the National Research Foundation (Unique Grant Numbers 118022 and 120383) and the Poliomyelitis Research Foundation.

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  1. Wits/SAMRC Antiviral Gene Therapy Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Private Bag 3, WITS, Johannesburg, 2050, South Africa

    Kristie Bloom, Fiona van den Berg & Patrick Arbuthnot

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  1. Kristie Bloom
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  2. Fiona van den Berg
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Correspondence to Kristie Bloom.

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KB is an associate editor of Gene Therapy.

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Bloom, K., van den Berg, F. & Arbuthnot, P. Self-amplifying RNA vaccines for infectious diseases. Gene Ther 28, 117–129 (2021). https://doi.org/10.1038/s41434-020-00204-y

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