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Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

By Franck Touret (200831), Magali Gilles (6540185), Raphaelle Klitting (6540188), Fabien Aubry (380458), Xavier de Lamballerie (95840) and Antoine Nougairède (213301)

Abstract

<p>Zika virus (ZIKV) has recently become dispersed throughout the tropics and sub-tropics, causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. In this study, we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared different constructs and confirmed the need to modify the cleavage site between the pre-peptide and prM protein. Genotypic characterization of the chimeras indicated that the emergence of compensatory mutations in the E protein was required to restore viral replicative fitness. Using an immunocompromised mouse model, we demonstrated that mice infected with the chimeric virus produced levels of neutralizing antibodies that were close to those observed following infection with ZIKV. Furthermore, pre-immunized mice were protected against viscerotropic and neuroinvasive disease following challenge with a heterologous ZIKV strain. These data provide a sound basis for the future development of this ZIKV vaccine candidate.</p

Topics: Genetics, Biotechnology, Immunology, Infectious Diseases, Virology, Biological Sciences not elsewhere classified, Infectious Subgenomic Amplicons, chimeric virus, protein, ZIKV epidemic strain, fever 17- D attenuated backbone Zika virus, fever 17- D attenuated backbone, Live Zika virus chimeric vaccine candidate, ISA, immunocompromised mouse model, ZIKV vaccine candidate, heterologous ZIKV strain
Year: 2019
DOI identifier: 10.6084/m9.figshare.7937837.v1
OAI identifier: oai:figshare.com:article/7937837
Provided by: FigShare
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