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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 2: scRNA-seq)

ABSTRACT: We performed an in-depth characterization and comparison of the immune system diversity and complexity in the spleen of conventional NRG-HIS mice and NFA2-HIS/Ftl3LG mice upon YFV-17D infection, a live-attenuated virus that induce that induce potent protective immunity in human. To do so, we employed Seq-Well, a recently developed platform for massively parallel single-cell RNA-Seq (scRNA-Seq), on splenocytes from NRG-HIS mice and NFA2-HIS/Flt3LG mice at six-weeks post YFV-17D infection. Our data provide an in-depth view of the cellular composition of the HIS in conventional and second-generation humanized mice. They also highlight the enhanced engraftment and functionality of the critical role of the myeloid and NK cell compartment in NFA2-HIS/Flt3LG mice, which is likely critical in promoting an enhanced transcriptomic, cellular and humoral response to YFV-17D.

ORGANISM(S): Homo sapiens

PROVIDER: GSE119750 | GEO | 2018/11/28

REPOSITORIES: GEO

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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses (Experiment 1: RNA-seq)

Project description:By taking advantage of the highly immunogenic live-attenuated yellow fever virus vaccine YFV-17D, we performed an in-depth comparison of transcriptomic responses in human vaccinees, conventional humanized mice, and second generation humanized mice. We demonstrate that selective expansion of human myeloid and natural killer cells in humanized mice promotes transcriptomic responses akin to those of human vaccinees

2018-11-28 | GSE119749 | GEO

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

Project description:We tested the effects of co-infection on vaccine response to YFV-17D. Groups of mice were divided into either Mock infected or Co-infected groups. Mock infected were housed in a biohazard facility and inoculated with PBS. Co-infected were infected sequentially with murine gammaherpesvirus-68, murine cytomegalovirus, influenza WSN, and Heligmosimoides polygyrus. Both mock and co-infected groups were challenged with Yellow Fever virus (YFV-17D). Day 0 is prior to YFV. Days 3, 7, and 21 were timepoints after YFV.

2016-03-22 | E-GEOD-79466 | biostudies-arrayexpress

Expression data from Rhesus immune cells responding to YFV

Project description:Immune response to infection involves the regulation of numerouse genes in numerous cell types. The number and type of genes that become differentially expressed in response to infection can result in very different pathophysiologic presentations and disease course. Wild type YFV and 17D despite having very few genetic differences result in very different disease outcomes in human and monkey hosts. We used microarrays to detail the global programme of gene expression of Rhesus macaque immune cells responding to both wild type and 17D strains of YFV. We identified distinct classes of gene expression as well as marked differences in differential gene expression between responses to 17D and wild type strains of YFV. Rhesus PBMC were isolated before and on day 3 of either vaccination with 17D or infection with wild type YFV with an n of 3 per group. Total RNA was extracted and hybridized on Affymetrix microarrays.

2014-10-22 | E-GEOD-51972 | biostudies-arrayexpress

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

Project description:We tested the effects of co-infection on vaccine response to YFV-17D.

2016-03-22 | GSE79466 | GEO

Expression data from Rhesus immune cells responding to YFV

2014-10-22 | GSE51972 | GEO

ATAC-seq analysis of human CD8 T cells specific for the NS4B-214 epitope in the Yellow fever vaccine YFV-17D strain

Project description:ATAC-seq analysis of human CD8 T cells specific for the NS4B-214 epitope in the Yellow fever vaccine YFV-17D strain

2017-12-13 | GSE101609 | GEO

Whole genome DNA methylation analysis of human CD8 T cell specific for the Yellow fever virus vaccine

Project description:Central questions regarding the origin of memory CD8 T cells, their turnover and longevity in vivo are not well-defined in humans. Here, we have used the highly efficacious live yellow fever virus vaccine (YFV-17D) to address these issues in the context of a primary acute viral infection. We interrogated genome-wide CpG methylation of YFV tetramer-specific CD8 T cells. These findings provide a better understanding of how memory CD8 T cells are formed and maintained in humans.

2017-12-13 | GSE75533 | GEO

Upregulation of USP18-ISG15 axis associates with protective immune responses and limited histopathology during SARS-CoV2 infection of the human lung

Project description:Investigating the intra-lung human immune responses to SARS-CoV-2, and how immune signatures temporally correlate to distinct histopathological manifestations of disease in the human lung, is not possible in human patients. While current non-human primate and rodent models have proven instrumental for evaluating COVID-19 treatments and vaccines, their non-human nature precludes faithful recapitulation of fundamental host-pathogen interactions and immunopathogenesis, particularly those governing severe COVID-19 disease. Here, using different mouse models engrafted with human lung tissues and human immune hematopoietic cells, we provide a unique picture of how differential human hematopoietic reconstitution, and immune signatures upon infection, correlate with distinct histopathology during SARS-CoV-2 infection. To do so, we engrafted pairs of human fetal lung xenografts (fLX) harboring lung-resident hematopoietic lineages into immunodeficient NRG mice (NRG-L), or into NRG-Flk2-/-Flt3LG mice co-engrafted with components of a human immune system (HIS-NRGF-L). Strikingly, while SARS-CoV-2 inoculation of NRG-L mice resulted in productive infection and extensive histopathological features typically observed in the lungs of severe COVID-19 patients, HIS-NRGF-L were able to rapidly control infection while preserving tissue integrity. Distinct histopathological outcomes were governed by differential proteomics and phospho-proteomics signatures and underscored the USP18-ISG15 pathway as a top immunomodulatory pathway defining effective control of viral replication and maintenance of tissue integrity in human lung tissue during SARS-CoV-2 infection. Our work highlights fLX-engrafted mice as a powerful platform to investigate the molecular basis that drives effective immune control of SARS-CoV-2, and open avenues for the development of innovative immunotherapies targeting the USP18-ISG15 pathway to alleviate severe COVID-19.

2022-04-14 | PXD025851 | Pride

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

Naïve-like Yellow-Fever specific CD8 T cells and reference CD8 T cell subsets in humans

Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine

2015-04-08 | GSE65804 | GEO

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