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Series GSE188575 Query DataSets for GSE188575
Status Public on Jan 06, 2023
Title MicroRNA profiling of extracellular vesicles isolated from rhesus macaques vaccinated with DNA/ALVAC/gp120 vaccine
Organism Macaca mulatta
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary 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.
Overall design Forty juvenile (young, average age 3.45 years, 0.545 SD) and twenty-eight adult (old, average age 7.98 years and 2.60 SD) macaques were assigned to four groups based on their major histocompatibility status, age, and weight. Thirteen young and seventeen old macaques were immunized twice with DNA-SIV at weeks 0 and 4. At weeks 8 and 12 all 30 macaques were boosted with intramuscular inoculations of 10^8 Plaque Forming Units (PFU) of recombinant ALVAC (vCP2432). At week 12, vaccinated macaques also received 200 μg each of SIVmac251 – M766 and SIVsmE660 – CG7V gp120-gD proteins formulated in alum Alhydrogel. Plasma collected at baseline from 7 young animals and 1 week following vaccination (week 13) from all vaccinated animals was used for extracellular vesicles (EVs) isolation. EVs were isolated from plasma as described previously (Thery, al.. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3, Unit 3 22 (2006)) with minor modifications. EVs isolated from plasma were processed by Exiqon, Inc. (Woburn, MA). The RNA was isolated from EVs by following a proprietary RNA isolation protocol. MicroRNA was used to generate the libraries and was subsequently sequenced on a NextSeq500 sequencing instrument (Illumina, Inc.).
Contributor(s) Bissa M, Galli V, Arakelyan A, Lobanov A, Nelson GW, Cam MC, Margolis L, Franchini G
Citation(s) 36732510
Submission date Nov 10, 2021
Last update date Apr 11, 2023
Contact name Massimiliano Bissa
Phone 2407606578
Organization name National Institutes of Health
Department NCI/CCR
Street address 9000 Rockville Pike, bldg 41/ room c303
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL21120 Illumina NextSeq 500 (Macaca mulatta)
Samples (37)
GSM5685842 T114_Old_DNA/DNA/ALVAC/ALVAC+gp120_week13
GSM5685843 T115_Old_DNA/DNA/ALVAC/ALVAC+gp120_week13
GSM5685844 T121_Old_DNA/DNA/ALVAC/ALVAC+gp120_week13
BioProject PRJNA779438
SRA SRP345462

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Supplementary file Size Download File type/resource
GSE188575_Normalized_Data.txt.gz 91.0 Kb (ftp)(http) TXT
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