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

• Published in: Vaccines (Basel) 2019-08, Vol.7 (3), p.96
• Main Authors: Zhong, Zifu, Portela Catani, João Paulo, Mc Cafferty, Séan, Couck, Liesbeth, Van Den Broeck, Wim, Gorlé, Nina, Vandenbroucke, Roosmarijn E, Devriendt, Bert, Ulbert, Sebastian, Cnops, Lieselotte, Michels, Johan, Ariën, Kevin K, Sanders, Niek N
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Clinical trials; Electroporation; Encephalitis; Genomes; Glycoproteins; IFNAR1 knockout mice; Immune response (cell-mediated); Immune response (humoral); Immunogenicity; Infectious diseases; Interferon; Molecular biology; mRNA; mRNA vaccines; Plasmids; Proteins; Replication; Robustness; self-replicating mRNA; Seroconversion; type I interferon response; Vaccines; Vector-borne diseases; Vectors (Biology); Viruses; Zika virus; Zika virus vaccine; β-Interferon
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines7030096

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 ). 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.