DC immunotherapy in HIV-1 infection induces a major blood transcriptome shift.
OBJECTIVE
This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles.


METHODS
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.
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: anna.degoede@radboudumc.nl.
Anna L
AL
de Goede
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.andeweg@erasmusmc.nl.
Arno C
AC
Andeweg
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: hj.vandenham@erasmusmc.nl.
Henk-Jan
HJ
van den Ham
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: m.a.bijl@erasmusmc.nl.
Maarten A
MA
Bijl
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: f.zaaraoui@erasmusmc.nl.
Fatiha
F
Zaaraoui-Boutahar
Erasmus Center for Biomics, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: w.vanijcken@erasmusmc.nl.
Wilfred F J
WF
van IJcken
Department of Medical Oncology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: sofie.wilgenhof@vub.ac.be.
Sofie
S
Wilgenhof
Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Medical School of the Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: joeri.aerts@vub.ac.be.
Joeri L
JL
Aerts
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: r.gruters@erasmusmc.nl.
Rob A
RA
Gruters
Department of Viroscience, Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: a.osterhaus@erasmusmc.nl.
Albert D M E
AD
Osterhaus
D016915:AIDS Vaccines; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000628:therapy; D008875:Middle Aged; D025341:Principal Component Analysis; D059467:Transcriptome; D014611:Vaccination; D019562:Viral Load
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D019496:Cancer Vaccines; D007252:Influenza Vaccines
Dendritic cell; Gene expression; HIV-1; Immunotherapy; Microarray; Vaccination