Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine
Zifu Zhong,
João Paulo 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,
Niek N. Sanders
Affiliations
Zifu Zhong
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
João Paulo Portela Catani
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
Séan Mc Cafferty
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
Liesbeth Couck
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
Wim Van Den Broeck
Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
Nina Gorlé
Barriers in Inflammation Lab, Department of Biomedical molecular biology, Faculty of Sciences, Ghent University, Technologiepark-Zwijnaarde 71, 9052 Zwijnaarde, Belgium
Roosmarijn E. Vandenbroucke
Barriers in Inflammation Lab, Department of Biomedical molecular biology, Faculty of Sciences, Ghent University, Technologiepark-Zwijnaarde 71, 9052 Zwijnaarde, Belgium
Bert Devriendt
Laboratory of Immunology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium
Sebastian Ulbert
Department of Immunology, Fraunhofer Institute for Cell Therapy and Immunology, Perlickstr. 1, 04103 Leipzig, Germany
Lieselotte Cnops
Unit of Neglected Tropical Diseases, Department of Clinical Sciences, Institute of Tropical Medicine, 2000 Antwerp, Belgium
Johan Michels
Virology Unit, Institute of Tropical Medicine, 2000 Antwerp, Belgium
Kevin K. Ariën
Virology Unit, Institute of Tropical Medicine, 2000 Antwerp, Belgium
Niek N. Sanders
Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820 Merelbeke, Belgium
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.
