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Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design Response by a Self-Amplifying RNA

Pepini, Timothy and Pulichino, Anne-Marie and Carsillo, Thomas and Carlson, Alicia and Sari-Sarraf, Farid and Ramsauer, Katrin and Debasitis, Jason and Maruggi, Giulietta and Otten, Gillis and Geall, Andrew and Yu, Dong and Ulmer, Jeffrey and Iavarone, Carlo (2017) Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design Response by a Self-Amplifying RNA. Journal of Immunology, 198.

Abstract

RNA-based vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part due to the potential to simplify how vaccines are made and facilitate a rapid response to newly emerging infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM) replicons encoding an antigen, formulated with a synthetic delivery system, and induce broad-based immune responses in preclinical animal models.
In our study, in vivo imaging shows that after the immunization SAM antigen expression has an initial gradual increase. Gene expression profiling in injection site tissues from mice immunized with SAM-based vaccine revealed an early and robust induction of type I IFN and IFN-stimulated responses at the site of injection, concurrent with the preliminary reduced SAM antigen expression. This SAM vaccine-induced type I IFN responses has the potential to provide an adjuvant effect on vaccine potency, or, conversely, it might establish a temporary state that limits the initial SAM-encoded antigen expression. To determine the role of the early type I interferon response, SAM vaccines were evaluated in IFN receptor knock-out mice. Our data indicate that minimizing the early type I interferon responses may be a useful strategy to increase primary SAM expression and the resulting vaccine potency. RNA sequence modification, delivery optimization or concurrent use of appropriate compounds might be some of the strategies to finalize this aim.

Item Type: Article
Date Deposited: 27 Apr 2017 00:45
Last Modified: 27 Apr 2017 00:45
URI: https://oak.novartis.com/id/eprint/31227

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