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ATAC-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine [study 2]

ABSTRACT: We analyzed innate and adaptive immune responses elicited by the V1-deleted DNA/ALVAC/gp120/alum vaccine in non-human primates. Following SIVmac251 challenge exposure, we observed reduced risk of SIV acquisition comparing vaccinated animals to controls, confirming th ability of this vaccine strategy in decreasing the risk of SIV acquisition against vaginal exposure. Transcriptome and chromatin accessibility in CD14+ cells were analyzed by RNA-seq and ATAC-seq. Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway correlated with vaccine efficacy. The efficacy of V1-delted DNA/ALVAC/gp120/alum vaccine, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Our data support the protective role for CREB1 expression in monocytes and posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE188879 | GEO | 2023/01/06

REPOSITORIES: GEO

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RNA-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine

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Transcriptomic profiling of young and old rhesus macaques vaccinated with DNA/ALVAC+gp120

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Transcriptomic profiling of rhesus macaques vaccinated with ALVAC-SIV/gp120 adjuvanted in Alum or MF59.

2016-05-29 | GSE72624 | GEO

Transcriptional profiling of macaques treated with ALVAC- and NYVAC-SIV+gp120 alum vaccines

Project description:Transcriptional profiling of macaques treated with ALVAC- and NYVAC-SIV+gp120 alum vaccines

| PRJNA575064 | ENA

Macaca mulatta

Project description:Transcriptomic profiling of rhesus macaques vaccinated with ALVAC-SIV/gp120 adjuvanted in Alum or MF59.

| PRJNA294508 | ENA

RNA-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine

Project description:RNA-seq profiling in CD14+ cells isolated from rhesus macaques vaccinated with V1-deleted DNA/ALVAC/gp120 vaccine

| PRJNA781227 | ENA

MicroRNA profiling of extracellular vesicles isolated from rhesus macaques vaccinated with DNA/ALVAC/gp120 vaccine

Project description:We contrasted innate and adaptive immune responses elicited by the DNA/ALVAC/gp120/alum vaccine in non-human primates differing in age. We performed several analyses. MicroRNA profiling in Extracellular Vesicles (EVs) isolated from plasma collected prior and 1 week following vaccination identified 109 miRNAs that differed significantly between age groups at the end of immunization. Several miRNAs correlated with risk of virus acquisition in young and old animals, but none remained significant following correction for FDR. In young animals, we identified 3 miRNAs which were modified by vaccination and correlated with decreased risk of SIV acquisition (unadjusted p-values). Of these three miRNAs, two, miR-139-5p and miR-29b-1-5p, were increased by vaccination, whereas one, mir 98, decreased by vaccination. MiR-139-5p has several validated targets, including: CXCR4, important for egress of CXCR4+ cells and monocytes from bone marrow and HIV entry in target T-cells; the cAMP-specific PDE4D gene which decreases CREB1-mediated transcription by degrading cAMP; and the IGF-1/AKT/Glut1 gene receptor, central for glucose utilization and cellular metabolism. The validated target of miR-29b-1-5p is the NF-kB pathway. Mir-98 has several validated targets, inhibits IL-10 production, modulates M1-M2 polarization of macrophages towards the M1 phenotype, and its CCL2-induced downregulation increases IL-6 production. These data suggest the importance of CREB1-mediated transcription in vaccine efficacy, identified in the study, is likely assisted by miR-139-5p targeting the cAMP-degrading PDE4D gene, and downregulation of the NF-kB pathway, targeted by miR-29b-1-5p.

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