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Article

Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine

1
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
2
Cancer Research Institute (CRIG), Ghent University, 9000 Ghent, Belgium
3
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
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Barriers in Inflammation Lab, Department of Biomedical molecular biology, Faculty of Sciences, Ghent University, Technologiepark-Zwijnaarde 71, 9052 Zwijnaarde, Belgium
5
VIB Center for Inflammation Research, VIB, Technologiepark-Zwijnaarde 71, 9052 Zwijnaarde, Belgium
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Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
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Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstr. 1, 04103 Leipzig, Germany
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Unit of Neglected Tropical Diseases, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium
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Virology Unit, Institute of Tropical Medicine, 2000 Antwerp, Belgium
10
Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors share senior authorship.
Vaccines 2019, 7(3), 96; https://doi.org/10.3390/vaccines7030096
Received: 8 July 2019 / Revised: 16 August 2019 / Accepted: 21 August 2019 / Published: 23 August 2019
(This article belongs to the Special Issue Immunization by Electroporation)
To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral and cellular immune responses in BALB/c and especially IFNAR1-/- C57BL/6 mice, resulting in a complete protection of the latter mice against ZIKV infection. In wild-type C57BL/6 mice, the vaccine resulted in very low seroconversion rates and antibody titers. The potency of the vaccine was inversely related to the dose of mRNA used in wild-type BALB/c or C57BL/6 mice, as robust type I interferon (IFN) response was determined in a reporter mice model (IFN-β+/Δβ-luc). We further investigated the inability of the sr-prM-E-mRNA ZIKV vaccine to raise antibodies in wild-type C57BL/6 mice and found indications that type I IFNs elicited by this naked sr-mRNA vaccine might directly impede the induction of a robust humoral response. Therefore, we assume that the efficacy of sr-mRNA vaccines after intradermal electroporation might be increased by strategies that temper their inherent innate immunogenicity. View Full-Text
Keywords: self-replicating mRNA; Zika virus vaccine; type I interferon response; IFNAR1 knockout mice self-replicating mRNA; Zika virus vaccine; type I interferon response; IFNAR1 knockout mice
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MDPI and ACS Style

Zhong, Z.; Portela Catani, J.P.; Mc Cafferty, S.; Couck, L.; Van Den Broeck, W.; Gorlé, N.; Vandenbroucke, R.E.; Devriendt, B.; Ulbert, S.; Cnops, L.; Michels, J.; Ariën, K.K.; Sanders, N.N. Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine. Vaccines 2019, 7, 96. https://doi.org/10.3390/vaccines7030096

AMA Style

Zhong Z, Portela Catani JP, Mc Cafferty S, Couck L, Van Den Broeck W, Gorlé N, Vandenbroucke RE, Devriendt B, Ulbert S, Cnops L, Michels J, Ariën KK, Sanders NN. Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine. Vaccines. 2019; 7(3):96. https://doi.org/10.3390/vaccines7030096

Chicago/Turabian Style

Zhong, Zifu, João P. Portela Catani, Séan Mc Cafferty, Liesbeth Couck, Wim Van Den Broeck, Nina Gorlé, Roosmarijn E. Vandenbroucke, Bert Devriendt, Sebastian Ulbert, Lieselotte Cnops, Johan Michels, Kevin K. Ariën, and Niek N. Sanders 2019. "Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine" Vaccines 7, no. 3: 96. https://doi.org/10.3390/vaccines7030096

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