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

Fehér C, Pastor-Lbáñez R, Leal L, Plana M, Arnedo M, Van den Ham HJ, Andeweg AC, Gruters RA, Díez-Fuertes F, Alcamí J, Aloy P, García F,
Vaccines, 2021, 9, 799

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.

Pubmed: 34358215
Direct link: 10.3390/vaccines9070799