Biology subjects

Mothe, B.

Publications and source records attributed to Mothe, B..

3 recordsLinked to original sources

bioRxiv2024

PD-1 blockade enhances HIV-1 vaccine-induced CD8+ T-cell responses in PWH early ART-treated

Current HIV-1 therapeutic vaccines do not generate T-cell immune responses in people with HIV-1 (PWH) able to eradicate the virus or to broadly control viral replication. The expression of inhibitory receptors (IRs) may limit vaccine efficacy by reducing specific effector functions in vaccine-induced T-cells. Recently, the clinical use of antibodies targeting IRs or immune checkpoint blockade (ICB) has demonstrated remarkable success in cancer remission. Therefore, there is a potential benefit of using ICB in PWH to improve the effectiveness of vaccine-induced T-cell responses. Here, we evaluated functional changes in vaccine-induced HIV-specific CD8 T-cell responses by in-vitro PD-1 and TIM-3 blockade during immune stimulation in PWH early ART-treated and vaccinated (Etvac). We compared Etvac to PWH early ART-treated (Et) and chronic ART-treated PWH (Chro). Our results demonstrate a significant increase in the functional responses of vaccine-induced HIV-1-specific CD8 T-cells upon PD-1 but not TIM-3 blockade in cellular proliferation, IFN{gamma} production, and activation. Although no effect was found in Et, similar findings were obtained in HIV-1-specific CD8 T-cells in Chro for combined PD-1/TIM-3 blockade. Moreover, we identify in Etvac a direct association between PD-1 expression in CD8+ T cells and in vitro response to anti-PD-1 treatment. Our findings support the potential adjuvant effect of PD-1 blockade to improve HIV-1 therapeutic vaccine efficacy in early ART-treated PWH for future human studies.

immunology↗

bioRxiv2021

Gut Microbiome Signatures Linked to HIV-1 Reservoir Size and Viremia Control

BackgroundThe 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. ResultsViremic 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, including methanogenesis and carbohydrate biosynthesis, were significantly decreased 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. ConclusionsThis 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.

immunology↗

bioRxiv2018

Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study

The impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the hosts genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.

genomics↗