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HIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates

dc.rights.licenseopenen_US
dc.contributor.authorFLAMAR, A. L.
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBONNABAU, Henri
dc.contributor.authorZURAWSKI, S.
dc.contributor.authorLACABARATZ, C.
dc.contributor.authorMONTES, M.
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorRICHERT, Laura
dc.contributor.authorWIEDEMANN, A.
dc.contributor.authorGALMIN, L.
dc.contributor.authorWEISS, D.
dc.contributor.authorCRISTILLO, A.
dc.contributor.authorHUDACIK, L.
dc.contributor.authorSALAZAR, A.
dc.contributor.authorPELTEKIAN, C.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
dc.contributor.authorZURAWSKI, G.
dc.contributor.authorLEVY, Y.
dc.date.accessioned2020-11-09T16:07:03Z
dc.date.available2020-11-09T16:07:03Z
dc.date.issued2018-11-30
dc.identifier.issn1932-6203 (Electronic) 1932-6203 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/12173
dc.description.abstractEnHIV-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. HIV-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. A therapeutic vaccine boosting cellular immunity against HIV-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for long-term drug therapies. An approach to elicit strong T cell-based immunity is to direct virus protein antigens specifically to dendritic cells (DCs), which are the key cell type for controlling immune responses. For eliciting therapeutic cellular immunity in HIV-1-infected individuals, we developed vaccines comprised of five T cell epitope-rich regions of HIV-1 Gag, Nef, and Pol (HIV5pep) fused to monoclonal antibodies that bind either, the antigen presenting cell activating receptor CD40, or the endocytic dendritic cell immunoreceptor DCIR. The study aimed to demonstrate vaccine safety, establish efficacy for broad T cell responses in both primed and naïve settings, and identify one candidate vaccine for human therapeutic development. The vaccines were administered to Rhesus macaques by intradermal injection with poly-ICLC adjuvant. The animals were either i) naïve or, ii) previously primed with modified vaccinia Ankara vector (MVA) encoding HIV-1 Gag, Pol, and Nef (MVA GagPolNef). In the MVA-primed groups, both DC-targeting vaccinations boosted HIV5pep-specific blood CD4+ T cells producing multiple cytokines, but did not affect the MVA-elicited CD8+ T cell responses. In the naive groups, both DC-targeting vaccines elicited antigen-specific polyfunctional CD4+ and CD8+ T cell responses to multiple epitopes and these responses were unchanged by a subsequent MVA GagPolNef boost. In both settings, the T cell responses elicited via the CD40-targeting vaccine were more robust and were detectable in all the animals, favoring further development of the CD40-targeting vaccine for therapeutic vaccination of HIV-1-infected individuals.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enSISTM
dc.title.enHIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates
dc.title.alternativePlos Oneen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pone.0207794en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30500852en_US
bordeaux.journalPLoS ONE
bordeaux.pagee0207794en_US
bordeaux.volume13en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue11en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamSISTM_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03160760
hal.version1
hal.date.transferred2021-03-05T13:51:20Z
hal.exporttrue
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