Please use this identifier to cite or link to this item: http://hdl.handle.net/10609/149195
Title: Plasma proteomic profiling identifies CD33 as a marker of HIV control in natural infection and after therapeutic vaccination
Author: Duran-Castells, Clara  
Prats, Anna  
Oriol-Tordera, Bruna  
Llano, Anuska  
Carrillo Galvez, Cristina
Martinez-Picado, Javier  
Ballana, Ester  
García Vidal, Edurne  
Clotet Sala, Bonaventura  
Muñoz-Moreno, Jose A.  
Hanke, Thomas  
Moltó Díaz, José Antonio  
Mothe, Beatriz  
Brander, Christian  
Ruiz Riol, Marta  
Citation: Duran-Castells, C. [Clara] Prats, A. [Ana]. Oriol-Tordera, B. [Bruna]. Llano, A. [Anuska]. Galvez, C. [Cristina]. Martinez-Picado, J. [Javier]. Ballana, E. [Ester]. Garcia-Vidal, E. [Edurne]. Clotet, B. [Bonaventura]. Muñoz-Moreno, J. [Jose A.]. Hanke, T. [Thomas]. Moltó, J. [José]. Mothe, B. [Beatriz]. Brander, C. [Christian]. Ruiz-Riol, M. [Marta]. (2023). Plasma proteomic profiling identifies CD33 as a marker of HIV control in natural infection and after therapeutic vaccination. eBioMedicine, 95, 1-15. doi: 10.1016/j.ebiom.2023.104732
Abstract: Background : Biomarkers predicting the outcome of HIV-1 virus control in natural infection and after therapeutic interventions in HIV-1 cure trials remain poorly defined. The BCN02 trial (NCT02616874), combined a T-cell vaccine with romidepsin (RMD), a cancer-drug that was used to promote HIV-1 latency reversal and which has also been shown to have beneficial effects on neurofunction. We conducted longitudinal plasma proteomics analyses in trial participants to define biomarkers associated with virus control during monitored antiretroviral pause (MAP) and to identify novel therapeutic targets that can improve future cure strategies. Methods: BCN02 was a phase I, open-label, single-arm clinical trial in early-treated, HIV infected individuals. Longitudinal plasma proteomes were analyzed in 11 BCN02 participants, including 8 participants that showed a rapid HIV-1 plasma rebound during a monitored antiretroviral pause (MAP-NC, ‘non-controllers’) and 3 that remained off ART with sustained plasma viremia <2000 copies/ml (MAP-C, ‘controllers’). Inflammatory and neurological proteomes in plasma were evaluated and integration data analysis (viral and neurocognitive parameters) was performed. Validation studies were conducted in a cohort of untreated HIV-1+ individuals (n = 96) and in vitro viral replication assays using an anti-CD33 antibody were used for functional validation. Findings: Inflammatory plasma proteomes in BCN02 participants showed marked longitudinal alterations. Strong proteome differences were also observed between MAP-C and MAP-NC, including in baseline timepoints. CD33/ Siglec-3 was the unique plasma marker with the ability to discriminate between MAPC-C and MAP-NC at all study timepoints and showed positive correlations with viral parameters. Analyses in an untreated cohort of PLWH confirmed the positive correlation between viral parameters and CD33 plasma levels, as well as PBMC gene expression. Finally, adding an anti-CD33 antibody to in vitro virus cultures significantly reduced HIV-1 replication and proviral levels in T cells and macrophages. Interpretation: This study indicates that CD33/Siglec-3 may serve as a predictor of HIV-1 control and as potential therapeutic tool to improve future cure strategies. Funding Spanish Science and Innovation Ministry (SAF2017-89726-R and PID2020-119710RB-I00), NIH (P01- AI131568), European Commission (GA101057548) and a Grifols research agreement.
Keywords: Control of HIV-1 infection
Plasma proteomics
Inflammation
Neurological function
Siglec-3/CD33
Kick and kill HIV cure strategy
DOI: https://doi.org/10.1016/j.ebiom.2023.104732
Document type: info:eu-repo/semantics/article
Version: info:eu-repo/semantics/publishedVersion
Issue Date: 2-Sep-2023
Publication license: http://creativecommons.org/licenses/by/4.0/es/  
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