Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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. 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Bruno Guy

PROVIDER: E-GEOD-22329 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Neisseria meningitidis remains an important cause of septicemia and meningitis. One of its major virulence traits is its ability to avoid killing by human serum. In the present work, the effect of growth phase (exponential versus stationary) and growth medium (THB versus Catlin) on normal human serum (NHS) sensitivity was assessed on two N. meningitidis serogroup B strains (MC58 and M982). Both strains were found to be dramatically more resistant to 20% NHS killing at early exponential phase than at stationary phase (73-100% survival after 1 to 2 hours of growth compared to less than 10% survival after 7 hours of growth). This growth phase effect was detected only when a rich medium (THB) was used while no such effect was observed using Catlin medium. KDO (2-Keto-3-deoxyoctulosonic acid) and sialic acid content were measured on serum-resistant and serum-sensitive bacteria and were found comparable, indicating that differences in LPS and capsule expression were not at the origin of the observed phenotypes. Transcriptome profiling using a PCR-array was used to compare serum-resistant and serum-sensitive bacteria. A set of 255 genes was found to be differentially expressed with 159 genes up-regulated in serum-resistant bacteria, among them 12 genes involved in glucose catabolism and 22 are known virulence factors. Overall, this study shows that serum-resistant phenotype of N. meningitidis could be obtained through modulating growth conditions. The nature of growth media and growth phases have a major impact on the ability of N. meningitidis to resist to NHS killing. Consequently, the present work underlines the critical importance of carefully controlling those parameters in any studies aimed at investigating the mechanisms and factors involved in N. meningitidis serum-resistance. All experiments were performed in dye swap. These experiments were performed with 2 strains of N. meningitidis serogroup B. In one set of experiments, the gene expression profile of bacteria cultured in THB medium during 7h was compared with the corresponding profile of bacteria cultured during 1h in the same medium. In a second set of experiments, the gene expression profile of 1 strain cultured in THB medium during 7h was compared with the corresponding profile of the same strain cultured in Catlin medium during 7h. 3 biological replicates were performed for each comparison.

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Innate signature induced in human mDCs by dengue vaccine candidates

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