Epigenetic landscape in the kick-and-kill therapeutic vaccine BCN02 clinical trial is associated with antiretroviral treatment interruption (ATI) outcome
Oriol-Tordera, Bruna (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Esteve-Codina, Anna (Universitat Pompeu Fabra)
Berdasco, Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Rosás-Umbert, Míriam (Aarhus University Hospital (Aarhus, Dinamarca))
Gonçalves, Elena (Sorbonne Université)
Duran-Castells, Clara (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Català-Moll, Francesc (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Llano Montero, Anuska (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Cedeño, Samandhy (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Puertas, Maria C. (CIBERINFEC)
Tolstrup, Martin (Aarhus University Hospital (Aarhus, Dinamarca))
Søgaard, Ole S. (Aarhus University Hospital (Aarhus, Dinamarca))
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol)
Martínez-Picado, Javier (Institució Catalana de Recerca i Estudis Avançats)
Hanke, Tomáš (Kumamoto University)
Combadiere, Behazine (Sorbonne Université)
Paredes, Roger (Institut Germans Trias i Pujol)
Hartigan-O'Connor, Dennis (UC Davis School of Medicine(Estats Units d'Amèrica))
Esteller, M (Universitat de Barcelona. Departament de Ciències Fisiològiques II)
Meulbroek, Michael (Projecte dels NOMS-Hispanosida, BCN Checkpoint (Barcelona))
Calle, M. Luz (Universitat de Vic)
Sánchez, Alex (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moltó, José (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ruiz-Riol, Marta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)

Date:	2022
Abstract:	European Commission. Horizon 2020 $a The BCN02-trial combined therapeutic vaccination with a viral latency reversing agent (romidepsin, RMD) in HIV-1-infected individuals and included a monitored antiretroviral pause (MAP) as an efficacy read-out identifying individuals with an early or late (< or > 4weeks) viral-rebound. Integrated -omics analyses were applied prior treatment interruption to identify markers of virus control during MAP. PBMC, whole-genome DNA methylation and transcriptomics were assessed in 14 BCN02 participants, including 8 Early and 4 Late viral-rebound individuals. Chromatin state, histone marks and integration analysis (histone-3 acetylation (H3Ac), viral load, proviral levels and HIV-specific T cells responses) were included. REDUC-trial samples (n = 5) were included as a control group for RMD administration alone. DNA methylation imprints after receiving the complete intervention discriminated Early versus Late viral-rebound individuals before MAP. Also, differential chromatin accessibility and histone marks at DNA methylation level were detected. Importantly, the differential DNA methylation positions (DMPs) between Early and Late rebounders before MAP were strongly associated with viral load, proviral levels as well as the HIV-specific T-cell responses. Most of these DMPs were already present prior to the intervention and accentuated after RMD infusion. This study identifies host DNA methylation profiles and epigenetic cascades that are predictive of subsequent virus control in a kick-and-kill HIV cure strategy. European Union Horizon 2020 Framework Programme for Research and Innovation under Grant Agreement N°681137-EAVI2020 and N°847943-MISTRAL, the Ministerio de Ciencia e Innovación (SAF2017_89726_R), and the National Institutes of Health-National Institute of Allergy and Infectious Diseases Program Grant 536 __ $f 681137-EAVI2020.
Grants:	European Commission. Horizon 2020 847943 Agencia Estatal de Investigación SAF2017_89726_R
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	HIV-1 vaccine ; Epigenetics ; DNA methylation
Published in:	EBioMedicine, Vol. 78 (march 2022) , ISSN 2352-3964

DOI: 10.1016/j.ebiom.2022.103956
PMID: 35325780

19 p, 3.7 MB

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