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Impact of two and three dose COVID-19 vaccination schedule on transcriptional, humoral and T cell immune response in previously heavily treated, single agent treated and naïve CLL patients

ABSTRACT: This study investigates the innate immune response to COVID-19 mRNA and vector-based vaccines in 15 patients with chronic lymphocytic leukemia (CLL). It assessed the innate and adaptive immune response of CLL patients after booster vaccination and generated a comprehensive transcriptome (mRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). Specifically, this investigation on a ‘3-dose’ cohort of heavily pretreated CLL patients, who had tested seronegative following a two-dose homologous vaccination (either BNT162b2 or ChAdOx1) and had received a third heterologous dose. A ‘2-dose’ cohort encompassed treatment-naïve or minimal pretreated CLL patients, who showed a serological immune response after the first vaccination and had received a second dose. Bulk mRNA-seq was conducted on PBMCs harvested prior to the vaccination and at days 2 and 7 post vaccination. The innate immune response observed in all patients was independent of the IgG antibody response. Expression of interferon-regulated genetic pathways was induced within two days after vaccination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201642 | GEO | 2022/10/21

REPOSITORIES: GEO

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BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant

Project description:SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

2022-06-21 | GSE174621 | GEO

Prior BNT162b vaccination enhances interferon-JAK-STAT regulated antiviral programs in hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant

Project description:SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of Peripheral Blood Mononuclear Cells. Four patients had received the first dose of BNT162b about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq revealed an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase had subsided by day 35. Expression of the genes encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins was increased in the vaccinated group. We also investigated the immune transcriptome in naïve individuals receiving their first dose of BNT162b and identified a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

2022-01-25 | GSE189039 | GEO

Deciphering transcriptome profiles of porcine PBMCs in response to porcine reproductive and respiratory syndrome virus vaccine

Project description:In vivo microarray study of global gene expression changes in peripheral blood mononuclear cells (PBMCs) of German Landrace pigs during the innate immune response to porcine reproductive and respiratory syndrome virus vaccination.

2017-02-14 | GSE78254 | GEO

Activation of Coagulation and Proinflammatory Pathways in Thrombosis with Thrombocytopenia Syndrome and Following COVID-19 Vaccination

Project description:Thrombosis with thrombocytopenia syndrome (TTS) is an extremely rare but potentially serious adverse event following immunization with the adenovirus vector-based COVID-19 vaccines Ad26.COV2.S (Janssen / Johnson & Johnson) or ChAdOx1 (AstraZeneca). However, no cases of TTS have been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States, suggesting that anti-vector immunity may reduce TTS risk. Here we show robust stimulation of platelet activation and coagulation pathways and innate immune pathways in patients with TTS but only transient activation of these pathways following vaccination. We evaluated proteomic profiles in 2 patients with TTS and transcriptomic and proteomic profiles in 20 people following an initial dose and a booster dose of Ad26.COV2.S and in 14 people who received the mRNA vaccines BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induced transient activation of platelet activation and coagulation pathways and innate proinflammatory pathways that resolved by day 7. TTS patients showed enhanced and sustained upregulation of these pathways, whereas a second immunization with Ad26.COV2.S or a reduced initial dose of Ad26.COV2.S resulted in lower activation of these pathways. These data provide insight into TTS pathogenesis and suggest a potential strategy for reducing TTS risk by lowering the dose of Ad26.COV2.S.

2023-10-13 | GSE220659 | GEO

Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

Project description:Understanding the immune responses to SARS-CoV-2 vaccination is critical to optimizing vaccination strategies for individuals with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here, we comprehensively analyzed innate and adaptive immune responses in 19 patients with SLE receiving a complete 2-dose Pfizer-BioNTech mRNA vaccine (BNT162b2) regimen compared with a control cohort of 56 healthy control (HC) volunteers. Patients with SLE exhibited impaired neutralizing antibody production and antigen-specific CD4+ and CD8+ T cell responses relative to HC. Interestingly, antibody responses were only altered in patients with SLE treated with immunosuppressive therapies, whereas impairment of antigen-specific CD4+ and CD8+ T cell numbers was independent of medication. Patients with SLE also displayed reduced levels of circulating CXC motif chemokine ligands, CXCL9, CXCL10, CXCL11, and IFN-γ after secondary vaccination as well as downregulation of gene expression pathways indicative of compromised innate immune responses. Single-cell RNA-Seq analysis reveals that patients with SLE showed reduced levels of a vaccine-inducible monocyte population characterized by overexpression of IFN-response transcription factors. Thus, although 2 doses of BNT162b2 induced relatively robust immune responses in patients with SLE, our data demonstrate impairment of both innate and adaptive immune responses relative to HC, highlighting a need for population-specific vaccination studies.

2024-03-01 | GSE250024 | GEO

Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus

2024-03-01 | GSE250023 | GEO

Genome-wide analysis of impact of B cells from the peripheral blood of chronic lymphocytic leukemia (CLL) patients versus B cells from healthy donors on CD14+ PBMCs from healthy donors

Project description:CD14+ cells in the PBMCs of CLL patients are converted into NLCs. CD14+ PBMCs from healthy donors when cultured with CLL cells give rise to differentiated cells called CD14CLL-cells, which are immunophenotypically similar to NLCs. CD14+ PBMCs from healthy donors when cultured with non-malignant B cells give rise to differentiated cells called CD14B-cells. Transcriptome wide analysis reveals genes involved in immune response to be significantly deregulated between CD14B-cells and CD14CLL-cells/NLCs.

2013-01-01 | GSE21838 | GEO

Genome-wide analysis of impact of B cells from the peripheral blood of chronic lymphocytic leukemia (CLL) patients versus B cells from healthy donors on CD14+ PBMCs from healthy donors

2013-01-01 | E-GEOD-21838 | biostudies-arrayexpress

Nanda2013 - B cell chronic lymphocytic leukemia A model with immune response

Project description:B cell chronic lymphocytic leukemia - A model with immune response Seema Nanda 1, , Lisette dePillis 2, and Ami Radunskaya 3, 1. Tata Institute of Fundamental Research, Centre for Applicable Mathematics, Bangalore 560065, India 2. Department of Mathematics, Harvey Mudd College, Claremont, CA 91711 3. Department of Mathematics, Pomona College, Claremont, CA, 91711, United States Abstract B cell chronic lymphocytic leukemia (B-CLL) is known to have substantial clinical heterogeneity. There is no cure, but treatments allow for disease management. However, the wide range of clinical courses experienced by B-CLL patients makes prognosis and hence treatment a significant challenge. In an attempt to study disease progression across different patients via a unified yet flexible approach, we present a mathematical model of B-CLL with immune response, that can capture both rapid and slow disease progression. This model includes four different cell populations in the peripheral blood of humans: B-CLL cells, NK cells, cytotoxic T cells and helper T cells. We analyze existing data in the medical literature, determine ranges of values for parameters of the model, and compare our model outcomes to clinical patient data. The goal of this work is to provide a tool that may shed light on factors affecting the course of disease progression in patients. This modeling tool can serve as a foundation upon which future treatments can be based. Keywords: NK cell, chronic lymphocytic leukemia, mathematical model, T cell., B-CLL.

2020-01-09 | MODEL2001090002 | BioModels

DC immunotherapy in HIV-1 infection induces a major blood transcriptome shift

Project description:Objective: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. Design: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. Methods: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. Results: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. Conclusions: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.

2015-04-30 | E-MTAB-3296 | biostudies-arrayexpress

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