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Innate signature induced in human mDCs by dengue vaccine candidates

ABSTRACT: Sanofi Pasteur is developing a tetravalent YFV 17D vaccine-based chimeric dengue vaccine (TV CYD), which is currently in clinical phase 3 development. DNA microarrays were used to assess the innate gene signature in human mDCs infected with the four CYDs alone or in combination, with a wild type dengue serotype 3 virus, or with a classically attenuated serotype 3 virus (VDV3) shown to be reactogenic in humans. We observed a very reproducible signature for each of the 4 CYDs, involving stimulation of Type I IFN genes and associated genes, together with genes encoding chemokines and other mediators involved in the initiation of adaptive responses. In contrast, the wt DEN3 virus induced a predominantly inflammatory profile, while VDV3 appeared to induce a blunted response, which may have contributed to its clinical outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE22329 | GEO | 2011/01/03

SECONDARY ACCESSION(S): PRJNA127659

REPOSITORIES: GEO

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Innate signature induced in human mDCs by dengue vaccine candidates

Project description:Sanofi Pasteur is developing a tetravalent YFV 17D vaccine-based chimeric dengue vaccine (TV CYD), which is currently in clinical phase 3 development. DNA microarrays were used to assess the innate gene signature in human mDCs infected with the four CYDs alone or in combination, with a wild type dengue serotype 3 virus, or with a classically attenuated serotype 3 virus (VDV3) shown to be reactogenic in humans. We observed a very reproducible signature for each of the 4 CYDs, involving stimulation of Type I IFN genes and associated genes, together with genes encoding chemokines and other mediators involved in the initiation of adaptive responses. In contrast, the wt DEN3 virus induced a predominantly inflammatory profile, while VDV3 appeared to induce a blunted response, which may have contributed to its clinical outcome. All oligochip experiments were performed in dye swap. For each experiment, the gene expression profile of infected cells was compared with the corresponding profile of uninfected cells. 2 biologicals replicates were performed for each virus.

2011-01-03 | E-GEOD-22329 | biostudies-arrayexpress

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Gene expression profiling of PBMC from coinfected or non-coinfected mice at d0, d3, d7, and d21 post YFV-17D challenge

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