Association of Transcriptomic Signatures of Inflammatory Response with Viral Control after Dendritic Cell-Based Therapeutic Vaccination in HIV-1 Infected Individuals

Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were ex...

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Bibliographic Details
Published in:Vaccines (Basel) 2021-07, Vol.9 (7), p.799
Main Authors: Fehér, Csaba, Pastor-lbáñez, Roque, Leal, Lorna, Plana, Montserrat, Arnedo, Mireia, van den Ham, Henk-Jan, Andeweg, Arno C., Gruters, Rob A., Díez-Fuertes, Francisco, Alcamí, José, Aloy, Patrick, García, Felipe
Format: Article
Language:English
Subjects:
Complement system
dendritic cell-based therapeutic HIV-1 vaccine
Dendritic cells
Deregulation
differential gene expression
DNA microarrays
E2F protein
Gene expression
Gene set enrichment analysis
HIV
Human immunodeficiency virus
Inflammation
Inflammatory response
Interferon
Interleukin 2
Interleukin 6
MicroRNAs
miRNA
mRNA
NF-κB protein
Patients
Peripheral blood mononuclear cells
Predictive control
Principal components analysis
Quality control
Ribonucleic acid
RNA
Signatures
Tumor necrosis factor
Vaccination
Vaccines
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Summary:Systems vaccinology has seldomly been used in therapeutic HIV-1 vaccine research. Our aim was to identify early gene ‘signatures’ that predicted virus load control after analytical therapy interruption (ATI) in participants of a dendritic cell-based HIV-1 vaccine trial (DCV2). mRNA and miRNA were extracted from frozen post-vaccination PBMC samples; gene expression was determined by microarray method. In gene set enrichment analysis, responders showed an up-regulation of 14 gene sets (TNF-alpha/NFkB pathway, inflammatory response, the complement system, Il6 and Il2 JAK-STAT signaling, among others) and a down-regulation of 7 gene sets (such as E2F targets or interferon alpha response). The expression of genes regulated by three (miR-223-3p, miR-1183 and miR-8063) of the 9 differentially expressed miRNAs was significantly down-regulated in responders. The deregulation of certain gene sets related to inflammatory processes seems fundamental for viral control, and certain miRNAs may be important in fine-tuning these processes.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines9070799