Association of transcriptomic signatures of inflammatory response with viral control after dendritic cell-based therapeutic vaccination in hiv-1 infected individuals

Csaba Fehér*, Roque Pastor-Lbáñez, Lorna Leal, Montserrat Plana, Mireia Arnedo, Henk Jan van den Ham, Arno C. Andeweg, Rob A. Gruters, Francisco Díez-Fuertes, José Alcamí, Patrick Aloy, Felipe García

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number799
JournalVaccines
Volume9
Issue number7
DOIs
Publication statusPublished - 19 Jul 2021

Bibliographical note

Funding Information:
Funding: This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018-096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Program/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study.

Funding Information:
This study was supported by the European Commission (grants: H2020-SC1-2016-RTD Proposal: 731626), the Spanish Ministry of Economy (MINECO) (grants: SAF2015-66193-R, RTI2018096309-B-I00), the Fondo de Investigación Sanitaria (FIS) PI15/00480, AC16/00051, and PI18/00699, amfAR Grant # 108821-55-RGRL, the Fondo Europeo para el Desarrollo Regional (FEDER), the SPANISH AIDS Research Network RD16/0025/0002–ISCIII–FEDER (RIS), and the CERCA Pro-gram/Generalitat de Catalunya SGR 615. F.G. has received the support of José María Segovia de Arana contracts. C.F. held a fellowship from “PhD4MD,” a Collaborative Research Training Programme for Medical Doctors financed by IRB Barcelona (Institute for Research in Biomedicine) and IDIBAPS (August Pi i Sunyer Biomedical Research Institute) during the study.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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