Immunogenicity and Protection Efficacy of a Naked Self-Replicating mRNA-Based Zika Virus Vaccine.
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.
['Zhong|Zifu|Z|', 'Portela Catani|João Paulo|JP|', 'Mc Cafferty|Séan|S|', 'Couck|Liesbeth|L|', 'Van Den Broeck|Wim|W|0000-0001-6683-5658', 'Gorlé|Nina|N|', 'Vandenbroucke|Roosmarijn E|RE|0000-0002-8327-620X', 'Devriendt|Bert|B|0000-0002-3222-8769', 'Ulbert|Sebastian|S|', 'Cnops|Lieselotte|L|', 'Michels|Johan|J|', 'Ariën|Kevin K|KK|', 'Sanders|Niek N|NN|0000-0003-4585-0343']
Zika virus vaccine self-replicating mRNA IFNAR1 knockout mice type I interferon response