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Immunogenicity and protection efficacy of a naked self-replicating mRNA-based Zika virus vaccine

 
: Zhong, Zifu; Portela Catani, Joao Paulo; Mc Cafferty, Séan; Couck, Liesbeth; Broeck, Wim van den; Gorlé, Nina; Vandenbroucke, Roosmarijn; Devriendt, Bert; Ulbert, Sebastian; Cnops, Lieselotte; Michels, Johan; Arien, Kevin K.; Sanders, Niek N.

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Volltext ()

Vaccines 7 (2019), Nr.3, Art. 96, 17 S.
ISSN: 2076-393X
Englisch
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IZI ()
self-replicating mRNA; Zika virus; Impfung; type 1 interferon repsonse; IFNAR1 knockout mice

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.

: http://publica.fraunhofer.de/dokumente/N-562088.html