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

Pastor-Ibáñez, Roque; Díez-Fuertes, Francisco; Sánchez-Palomino, Sonsoles; Alcamı́, José; Plana, Montserrat; Torrents, David; Leal, Lorna; García, Felipe

doi:10.3390/vaccines9070694

Cited by 12 publications

(13 citation statements)

References 41 publications

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“…Also, elite controllers, who spontaneously control HIV replication without ART, showed higher gut microbial richness with a metabolic profile resembling that of HIV-uninfected adults [ 50 ] and increased Th17 cells in the gut mucosa compared to ART-treated patients [ 51 ]. In line with our results, a recent study showed enriched levels of Bacteroidetes genera, such as Bacteroides and Prevotella , in patients with sustained HIV control during ART interruption, after receiving dendritic cells-based HIV-1 immunization [ 52 ]. Moreover, additional evidence on HIV virologic controllers receiving a TLR7 agonist before ART interruption with baseline enrichment in P. copri and negative association between abundance of Ruminococcus gnavus and time to viral rebound suggested a potential impact of certain microbiome species on HIV persistence [ 53 ].…”

Section: Discussionsupporting

confidence: 91%

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

et al. 2022

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Background The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial. Results Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size. Conclusions The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.

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Section: Discussionsupporting

confidence: 91%

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

et al. 2022

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“…These studies have reported inconsistent results. In humans, the administration of oral typhoid or an intranodal and intramuscularly human immunodeficiency virus (HIV)-1 vaccine was not reported to significantly affect the composition of the intestinal microbiota one week to several months after vaccination 12 , 21 , 22 . The first two studies used amplicon sequencing, while the third used shotgun metagenomic sequencing.…”

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confidence: 99%

The immunological interplay between vaccination and the intestinal microbiota

Zimmermann

2023

npj Vaccines

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“…The effect of vaccine administration on the intestinal microbiota has gathered even less attention. Previous works investigating the effects of HIV-1 14,15 and oral typhoid 16 vaccines on the human gut microbiota reported no discernible perturbations of the microbial community structure induced by vaccination. In contrast, an increase in the Firmicutes/Bacteroidetes ratio following HIV-1 DNA/ protein immunization was observed in the rectal microbiome of non-human primates 17 .…”

Section: Introductionmentioning

confidence: 79%

Vaccination with an HIV T-cell immunogen induces alterations in the mouse gut microbiota

Borgognone

Elizalde-Torrent

Casadellà

et al. 2022

npj Biofilms Microbiomes

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The gut microbiota is emerging as a crucial factor modulating vaccine responses; however, few studies have investigated if vaccines, in turn, can alter the microbiota and to what extent such changes may improve vaccine efficacy. To understand the effect of T-cell vaccination on the gut microbiome, we administered an HIV-1 T-cell immunogen (HTI arm) or PBS (control, Mock arm) to C57Bl/6 mice following a heterologous prime-boost scheme. The longitudinal dynamics of the mice gut microbiota was characterized by 16 S ribosomal RNA sequencing in fecal samples collected from cages, as well as from three gut sections (cecum, small and large intestine). Serum and spleen cells were obtained at the last time point of the study to assess immune correlates using IFNγ ELISPOT and cytokine Luminex® assays. Compared with Mock, HTI-vaccinated mice were enriched in Clostridiales genera (Eubacterium xylanophilum group, Roseburia and Ruminococcus) known as primary contributors of anti-inflammatory metabolites, such as short-chain fatty acids. Such shift was observed after the first HTI dose and remained throughout the study follow-up (18 weeks). However, the enriched Clostridiales genera were different between feces and gut sections. The abundance of bacteria enriched in vaccinated animals positively correlated with HTI-specific T-cell responses and a set of pro-inflammatory cytokines, such as IL-6. This longitudinal analysis indicates that, in mice, T-cell vaccination may promote an increase in gut bacteria known to produce anti-inflammatory molecules, which in turn correlate with proinflammatory cytokines, suggesting an adaptation of the gut microbial milieu to T-cell-induced systemic inflammation.

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

Cited by 12 publications

References 41 publications

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

The immunological interplay between vaccination and the intestinal microbiota

Vaccination with an HIV T-cell immunogen induces alterations in the mouse gut microbiota

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