Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine

Therapeutic vaccines based on dendritic cells offer a good approach to HIV-specific T-cell responses and partial control of the viral load after antiretroviral therapy interruption. The aim of the present study was to identify mRNA expression profiles and to assess the impact of the gut microbiome c...

Full description

Bibliographic Details
Main Authors: Roque Pastor-Ibáñez, Francisco Díez-Fuertes, Sonsoles Sánchez-Palomino, Jose Alcamí, Montserrat Plana, David Torrents, Lorna Leal, Felipe García
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/7/694
_version_ 1797528862110777344
author Roque Pastor-Ibáñez
Francisco Díez-Fuertes
Sonsoles Sánchez-Palomino
Jose Alcamí
Montserrat Plana
David Torrents
Lorna Leal
Felipe García
author_facet Roque Pastor-Ibáñez
Francisco Díez-Fuertes
Sonsoles Sánchez-Palomino
Jose Alcamí
Montserrat Plana
David Torrents
Lorna Leal
Felipe García
author_sort Roque Pastor-Ibáñez
collection DOAJ
description Therapeutic vaccines based on dendritic cells offer a good approach to HIV-specific T-cell responses and partial control of the viral load after antiretroviral therapy interruption. The aim of the present study was to identify mRNA expression profiles and to assess the impact of the gut microbiome composition for predicting the viral load control after antiretroviral therapy interruption. We enrolled 29 patients to receive either placebo or a monocyte-derived dendritic cell vaccine. Patients with a decrease in their viral load of >0.5 log<sub>10</sub> copies/mL by 12 weeks after antiretroviral therapy interruption were considered responders. In total, 66 genes were considered differentially expressed between responders and non-responders. Enrichment analysis revealed several upregulated pathways involved in the host defense response to a virus via the type I interferon signaling pathway. Regarding the gut microbiota, responders showed enriched levels of Bacteroidetes (<i>p</i> < 0.005) and Verrucomicrobia (<i>p</i> = 0.017), while non-responders were enriched with Tenericutes (<i>p</i> = 0.049) and Actinobacteria (<i>p</i> < 0.005). We also found important differences at the genus level. However, we did not discover any effect of the dendritic cell vaccine on the transcriptome or the gut microbiota. An alternative analysis did characterize that the microbiota from responders were associated with the metabolic production of short-chain fatty acids, which are key metabolites in the regulation of intestinal homeostasis. The evidence now consistently shows that short-chain fatty acid depletion occurs in HIV-infected individuals receiving antiretroviral treatment.
first_indexed 2024-03-10T10:05:21Z
format Article
id doaj.art-3183044bb0c343aa812d829a49f36d58
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-03-10T10:05:21Z
publishDate 2021-06-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj.art-3183044bb0c343aa812d829a49f36d582023-11-22T01:34:31ZengMDPI AGVaccines2076-393X2021-06-019769410.3390/vaccines9070694Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic VaccineRoque Pastor-Ibáñez0Francisco Díez-Fuertes1Sonsoles Sánchez-Palomino2Jose Alcamí3Montserrat Plana4David Torrents5Lorna Leal6Felipe García7AIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainInstituto de Salud Carlos III, Ctra. de Pozuelo, 28, Majadahonda, 28222 Madrid, SpainAIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainAIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainAIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainComputational Genomics Groups, Barcelona Supercomputing Center (BSC), Plaça d’Eusebi Güell, 1-3, 08034 Barcelona, SpainAIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainAIDS Research Group, IDIBAPS, Hospital Clinic, University of Barcelona, 170, 08036 Barcelona, SpainTherapeutic vaccines based on dendritic cells offer a good approach to HIV-specific T-cell responses and partial control of the viral load after antiretroviral therapy interruption. The aim of the present study was to identify mRNA expression profiles and to assess the impact of the gut microbiome composition for predicting the viral load control after antiretroviral therapy interruption. We enrolled 29 patients to receive either placebo or a monocyte-derived dendritic cell vaccine. Patients with a decrease in their viral load of >0.5 log<sub>10</sub> copies/mL by 12 weeks after antiretroviral therapy interruption were considered responders. In total, 66 genes were considered differentially expressed between responders and non-responders. Enrichment analysis revealed several upregulated pathways involved in the host defense response to a virus via the type I interferon signaling pathway. Regarding the gut microbiota, responders showed enriched levels of Bacteroidetes (<i>p</i> < 0.005) and Verrucomicrobia (<i>p</i> = 0.017), while non-responders were enriched with Tenericutes (<i>p</i> = 0.049) and Actinobacteria (<i>p</i> < 0.005). We also found important differences at the genus level. However, we did not discover any effect of the dendritic cell vaccine on the transcriptome or the gut microbiota. An alternative analysis did characterize that the microbiota from responders were associated with the metabolic production of short-chain fatty acids, which are key metabolites in the regulation of intestinal homeostasis. The evidence now consistently shows that short-chain fatty acid depletion occurs in HIV-infected individuals receiving antiretroviral treatment.https://www.mdpi.com/2076-393X/9/7/694microbiotatranscriptomicsdendritic cellvaccineantiretroviralHIV-1
spellingShingle Roque Pastor-Ibáñez
Francisco Díez-Fuertes
Sonsoles Sánchez-Palomino
Jose Alcamí
Montserrat Plana
David Torrents
Lorna Leal
Felipe García
Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
Vaccines
microbiota
transcriptomics
dendritic cell
vaccine
antiretroviral
HIV-1
title Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
title_full Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
title_fullStr Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
title_full_unstemmed Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
title_short Impact of Transcriptome and Gut Microbiome on the Response of HIV-1 Infected Individuals to a Dendritic Cell-Based HIV Therapeutic Vaccine
title_sort impact of transcriptome and gut microbiome on the response of hiv 1 infected individuals to a dendritic cell based hiv therapeutic vaccine
topic microbiota
transcriptomics
dendritic cell
vaccine
antiretroviral
HIV-1
url https://www.mdpi.com/2076-393X/9/7/694
work_keys_str_mv AT roquepastoribanez impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT franciscodiezfuertes impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT sonsolessanchezpalomino impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT josealcami impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT montserratplana impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT davidtorrents impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT lornaleal impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine
AT felipegarcia impactoftranscriptomeandgutmicrobiomeontheresponseofhiv1infectedindividualstoadendriticcellbasedhivtherapeuticvaccine