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Gene Expression Signatures Associated With Immune and Virological Responses to Therapeutic Vaccination With Dendritic Cells in HIV-Infected Individuals

dc.rights.licenseopenen_US
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorHEJBLUM, Boris
ORCID: 0000-0003-0646-452X
IDREF: 189970316
dc.contributor.authorHOCINI, Hakim
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBONNABAU, Henri
dc.contributor.authorSKINNER, Jason
dc.contributor.authorMONTES, Monica
dc.contributor.authorLACABARATZ, Christine
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorRICHERT, Laura
dc.contributor.authorPALUCKA, Karolina
dc.contributor.authorBANCHEREAU, Jacques
dc.contributor.authorLÉVY, Yves
dc.date.accessioned2020-07-24T08:59:26Z
dc.date.available2020-07-24T08:59:26Z
dc.date.issued2019-04-24
dc.identifier.issn16643224en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10668
dc.description.abstractEnThe goal of HIV therapeutic vaccination is to induce HIV-specific immune response able to control HIV replication. We previously reported that vaccination with ex vivo generated Dendritic Cells (DC) loaded with HIV-lipopeptides in HIV-infected patients (n = 19) on antiretroviral therapy (ART) was well-tolerated and immunogenic. Vaccine-elicited HIV-specific T cell responses were associated with improved control of viral replication following antiretroviral interruption (ATI from w24 to w48). We show an inverse relationship between HIV-specific responses (production of IL-2, IL-13, IL-21, IFN-g, CD4 polyfunctionality, i.e., production of at least two cytokines) and the peak of viral load during ATI. Here we have performed an integrative systems vaccinology analysis including: (i) post vaccination (w16) immune responses assessed by cytometry, cytokine secretion, and Interferon-γ ELISPOT assays; (ii) whole blood and cellular gene expression measured during vaccination; and (iii) viral parameters following ATI, with the objective to disentangle the relationships between these markers and to identify vaccine signatures. During vaccination, 69 gene expression modules out of 260 varied significantly including (by order of significance) modules related to inflammation (Chaussabel Modules M3.2, M4.13, M4.6, M5.7, M7.1, M4.2), plasma cells (M4.11) and T cells (M4.1, 4.15). Cellular immune responses were positively correlated to genes belonging to T cell functional modules (M4.1, M4.15) at w16 and negatively correlated to genes belonging to inflammation modules (M7.1, M5.7, M3.2, M4.13, M4.2). More specifically, we show that prolonged increased abundance of inflammatory gene pathways related to toll-like receptor signaling (especially TLR4) are associated with both lower vaccine immune responses and control of viral replication post ATI. Further comparison of DC vaccine gene signatures with previously reported non-HIV vaccine signatures, such as flu and pneumococcal vaccines, revealed common pathways across vaccines. Overall, these results show that too long duration and too high intensity of vaccine inflammatory responses hamper the magnitude of effector responses. [ABSTRACT FROM AUTHOR] Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subject.enSISTM
dc.title.enGene Expression Signatures Associated With Immune and Virological Responses to Therapeutic Vaccination With Dendritic Cells in HIV-Infected Individuals
dc.title.alternativeFront Immunolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.3389/fimmu.2019.00874
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
bordeaux.journalFrontiers in Immunologyen_US
bordeaux.volume10en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamHEALTHY_BPH
bordeaux.teamSISTM_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03161837
hal.version1
hal.date.transferred2021-03-15T09:26:48Z
hal.exporttrue
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