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

Research output: Contribution to journalA1: Web of Science-article

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Abstract

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.

Original languageEnglish
Article number96
JournalVaccines
Volume7
Issue number3
Number of pages17
ISSN2076-393X
DOIs
Publication statusPublished - 2019

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