DC immunotherapy in HIV-1 infection induces a major blood transcriptome shift. Issue 25 (9th June 2015)

• Record Type: Journal Article
• Authors: de Goede, Anna L.; Andeweg, Arno C.; van den Ham, Henk-Jan; Bijl, Maarten A.; Zaaraoui-Boutahar, Fatiha; van IJcken, Wilfred F.J.; Wilgenhof, Sofie; Aerts, Joeri L.; Gruters, Rob A.; Osterhaus, Albert D.M.E.
• Is Part Of: Vaccine. Volume 33:Issue 25(2015)
• Page Start: 2922
• Page End: 2929
• Publication Date: 2015-06-09
• Subjects: HIV-1 -- Microarray -- Gene expression -- Vaccination -- Immunotherapy -- Dendritic cell; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.04.047
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: DC-based immunotherapy in HIV changes the PBMC transcriptome. The transcriptome became enriched for T-cell skewed immune markers. Interruption of cART did not change the established transcriptome shift. The transcriptome consisted of signatures of inflammation and immune exhaustion. The net result of these signatures was a modest decrease in plasma viral load. Abstract: Objective: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. Design: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. Methods: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. Results: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. Conclusions: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.