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Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

ABSTRACT: Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

PROVIDER: PRJNA490175 | ENA |

REPOSITORIES: ENA

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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

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

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

| PRJNA490176 | ENA

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

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

| PRJNA490177 | ENA

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

Project description: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.

2018-11-28 | GSE119750 | GEO

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.

Project description: Not available

| S-EPMC6262001 | biostudies-literature

Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-11-28 | GSE119751 | GEO

Vaccine Induces Dual T cell plus NK cell Attack against Resistant Tumors

Project description:Here we report a cancer vaccine that induced a coordinated attack by diverse T cell and NK cell populations. The vaccine targeted the MICA and MICB (MICA/B) stress proteins expressed by many human cancers due to DNA damage. MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumors evade immune recognition by proteolytic MICA/B cleavage. Vaccine-induced antibodies increased the density of MICA/B proteins on the surface of tumor cells by inhibiting proteolytic shedding, increased presentation of tumor antigens by dendritic cells to T cells, and enhanced the cytotoxic function of NK cells. Importantly, this vaccine maintained efficacy against MHC-I deficient tumors resistant to cytotoxic T cells through the coordinated action of NK cells and CD4 T cells. The vaccine was also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumors inhibited the later outgrowth of metastases. This vaccine design enables protective immunity even against tumors with common escape mutations.

2022-03-25 | GSE181997 | GEO

Single-cell RNA-sequencing of human innate lymphoid cells (ILCs) and natural killer (NK) cells in the vascular and tissue compartment of the lung in MISTRG humanized mice

Project description:ILCs and NK cells are innate immune cells that act as sentinels of healthy tissue function. However, it is largely unknown how ILCs and NK cells are recruited into distinct tissue niches and how they adapt to specific anatomical niches within tissues. Using an in-vivo model for human immune cells (MISTRG humanized mice), we determined the gene signatures of human ILCs and NK cells in the vascular and tissue niche of the lung by single-cell RNA-sequencing.

2023-06-27 | GSE217706 | GEO

NK cell expansion on uAPC helper cells

Project description:Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK cells expressing chimeric antigen receptors (CARs) have enhanced effector function against various type of cancer and are attractive contenders for the next generation of cancer immunotherapies. However, a number of factors have hindered the application of NK cells for cellular therapy, including their poor in vitro growth kinetics and relatively low starting percentages within the mononuclear cell fraction of peripheral blood or cord blood (CB). To overcome these limitations, we genetically-engineered human leukocyte antigen (HLA)-A- and HLA-B- K562 cells to enforce the expression of CD48, 4-1BBL, and membrane-bound IL-21 (mbIL21), creating a universal antigen presenting cell (uAPC) capable of stimulating their cognate receptors on NK cells. We have shown that uAPC can drive the expansion of both non-transduced (NT) and CAR-transduced CB derived NK cells by greater than 900-fold in 2 weeks of co-culture with excellent purity (>99.9%) and without indications of senescence/exhaustion. We confirmed that uAPC-expanded research- and clinical-grade NT and CAR-transduced NK cells have higher metabolic fitness and display enhanced effector function against tumor targets compared to the corresponding cell fractions cultured without uAPCs. This novel approach allowed the expansion of highly pure GMP-grade CAR NK cells at optimal cell numbers to be used for adoptive CAR NK cell-based cancer immunotherapy.

2020-12-06 | GSE162716 | GEO

SARS-CoV2 manipulates multiple NK ligands and inhibits NK activation, but this can be overcome by ADNKA, which is strongly activated by non-Spike targeting antibodies

Project description:SARS-CoV2 is recognised the antagonise the interferon response, and functioning interferon responses are critical in determining the severity of disease. However, whether the virus antagonises cellular immunity has not been determined. We used quantitative plasma membrane proteomics in lung epithelial cells to investigate viral manipulation of cell surface ligands, revealing that SARS-CoV2 does not affect HLA-I levels, but downregulates B7-H6, MICA, ULBP2, and Nectin1. Downregulation of these activating NK ligands correlated with a reduction in NK activation in response to infected cells. However, this activation could be overcome through antibody dependent NK activation (ADNKA). Surprisingly, monoclonal anti-spike antibodies were relatively poor activators of ADNKA, however expression of additional viral proteins, including ORF3a and Nucleocapsid, also led to NK activation following addition of antibodies. Furthermore, depletion of Spike antibodies revealed that while the neutralising response was dominated by anti-spike antibodies, these played a minor role in ADNKA against infected cells. Finally, we showed that anti-spike antibodies do mediate ADNKA following vaccination, but that by relying solely on spike to prime ADNKA, this response is considerably weaker than the responses seen following natural infection, and are not boosted by a second vaccine dose. Thus, the addition of extra viral proteins such as nucleocapsid to vaccines may recruit additional effector functions more strongly, reducing the impact of spike mutations on vaccine escape.

2022-05-26 | PXD025000 | Pride

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