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Preclinical efficacy of a live vesicular stomatitis virus-based Lassa virus vaccine candidate advanced for human clinical trials

ABSTRACT: Preclinical efficacy of a live vesicular stomatitis virus-based Lassa virus vaccine candidate advanced for human clinical trials

PROVIDER: PRJNA1031656 | ENA |

REPOSITORIES: ENA

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Preclinical efficacy of a live vesicular stomatitis virus-based Lassa virus vaccine candidate advanced for human clinical trials

Project description:We advanced a promising experimental vaccine for immunizing against the Lassa virus surface glycoprotein as a candidate for human trials. Preclinical evaluation of the vaccine candidate based on a live vesicular stomatitis virus (VSV) vector showed that it was highly efficacious in cynomolgus macaques consistent with earlier research studies, and that the animals developed serum antibodies that could mediate antiviral effector functions including direct neutralization of virus infectivity. As part of this evaluation, we analyzed whole-blood transcriptomes from each study subject prior to vaccination and at 1 day and 3 days post-vaccination.

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miRNA profiling of mouse primary peritoneal macrophages infected with vesicular stomatitis virus (VSV)

Project description:To investigate whether and what miRNAs expression might be regulated by VSV (vesicular stomatitis virus?) challenge, we analyzed the miRNA expression profile of mouse primary peritoneal macrophages infected with VSV by using an array-based miRNA profiling. After the infection of VSV at MOI 10 for 48 h, the array revealed that many miRNAs were up-regulated in macrophages?

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Analysis of global gene expression profiles of hPAF1 deficient A549 cells during infection with H1N1 influenza A virus or vesicular stomatitis virus (VSV)

Project description:Viral infection is commonly associated with virus-driven hijacking of host proteins. We describe a novel mechanism by which influenza virus impacts host cells through the interaction of influenza NS1 protein with the infected cell epigenome. We show that the NS1 protein of influenza A H3N2 targets the transcription elongation PAF1 complex (hPAF1C). We demonstrate that binding of NS1 to hPAF1C results in suppression of hPAF1C-mediated transcriptional elongation. More importantly,in the following data sets, we show that hPAF1 plays a crucial role in the antiviral response. Loss of hPAF1C reduces antiviral gene expression and reduces inducible transcription of target genes after stimulation with viral RNA analogue poly(I:C), vesicular stomatitis virus (VSV), exogenous recombinant IFN(beta) and influenza virus (H1N1). This study underscores the importance of hPAF1C in controlling inducible antiviral gene expression. Untreated (no siRNA), control siRNA-treated and hPAF1 siRNA-treated A549 cells were stimulated with A/Puerto Rico/8/1934 influenza virus (H1N1) or vesicular stomatitis virus (VSV). Total RNA was isolated with the Qiagen RNeasy mini kit. 200ng of total RNA per sample was used to prepare biotin-labeled RNA using MessageAmp™ Premier RNA Amplification Kit (Applied Biosystems) and hybridized to HumanHT-12 v4 Expression BeadChips (Illumina). Data analysis was performed using the GeneSpring GX11.0 software (Agilent Technologies). 3 biological replicates per condition

2012-02-15 | E-GEOD-35266 | biostudies-arrayexpress

Analysis of global gene expression profiles of hPAF1 deficient A549 cells during infection with H1N1 influenza A virus or vesicular stomatitis virus (VSV)

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Next-generation sequencing of three memory OT-I cell subsets from mice infected with vesicular stomatitis virus

Project description:Purpose: RNA-seq analysis of three memory OT-I cell subsets (from a Klrg1-Cre fate reporter mouse model) isolated from the spleen of C57BL/6 mice infected with vesicular stomatitis virus. The hypothesis tested in the present study was that KLRG1+ effector CD8 T lymphocytes differentiate into KLRG1- memory CD8 T lymphocytes and provide long-lasting immunity against infectious diseases and malignancies. Methods: Total RNA was obtained from FACS-purified OT-I cell subsets isolated from spleen 70 days post infection with ovalbumin-expressing vesicular stomatitis virus (VSV-OVA) (experiment 3). Results: Using RNA-seq technology, we performed genome-wide transcriptional profiling of three memory OT-I cells (KLRG1+ Reporter+, KLRG1- Reporter+ (exKLRG1) and KLRG1- Reporter-) and identified 36 genes differentially expressed (> 1.5-fold) between exKLRG1 and KLRG1- Reporter- memory OT-I cells, and 132 differentially expressed genes between exKLRG1 and KLRG1+ Reporter+ memory OT-I cells. We then confirmed the expression of 15 genes/molecules by qRT-PCR and/or flow cytometry. Conclusions: Our study represents the first fate mapping analysis of KLRG1+ effector OT-I cells, demonstrates that KLRG1+ effector OT-I cells differentiate into all memory T cell lineages thereby promoting protective immunity. RNA-seq also identified CX3CR1 as a marker of circulating exKLRG1 early memory OT-I cells.

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2021-12-26 | GSE191225 | GEO

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