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Innate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination

dc.rights.licenseopenen_US
dc.contributor.authorGONCALVES, E.
dc.contributor.authorBONDUELLE, O.
dc.contributor.authorSORIA, A.
dc.contributor.authorLOULERGUE, P.
dc.contributor.authorROUSSEAU, A.
dc.contributor.authorCACHANADO, M.
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBONNABAU, Henri
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
dc.contributor.authorTCHITCHEK, N.
dc.contributor.authorBEHILLIL, S.
dc.contributor.authorVAN DER WERF, S.
dc.contributor.authorVOGT, A.
dc.contributor.authorSIMON, T.
dc.contributor.authorLAUNAY, O.
dc.contributor.authorCOMBADIERE, B.
dc.date.accessioned2020-06-23T07:17:58Z
dc.date.available2020-06-23T07:17:58Z
dc.date.issued2019-03-01
dc.identifier.issn1558-8238 (Electronic) 0021-9738 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/8083
dc.description.abstractEnBACKGROUND: Systems vaccinology allows cutting-edge analysis of innate biomarkers of vaccine efficacy. We have been exploring novel strategies to shape the adaptive immune response, by targeting innate immune cells through novel immunization routes. METHODS: This randomized phase I/II clinical study (n=60 healthy subjects aged 18-45 years old) used transcriptomic analysis to discover early biomarkers of immune response quality after transcutaneous (t.c.), intradermal (i.d.), and intramuscular (i.m.) administration of a trivalent influenza vaccine (TIV season 2012-2013) (1:1:1 ratio). Safety and immunogenicity (hemagglutinin inhibition (HI), microneutralization (MN) antibodies and CD4, CD8 effector T cells) were measured at baseline Day (D)0 and at D21. Blood transcriptome was analyzed at D0 and D1. RESULTS: TIV-specific CD8+GranzymeB+(GRZ) T cells appeared in more individuals immunized by the t.c. and i.d. routes, while immunization by the i.d. and i.m. routes prompted high levels of HI antibody titers and MN against A/H1N1 and A/H3N2 influenza viral strains. The early innate gene signature anticipated immunological outcome by discriminating two clusters of individuals with either distinct humoral or CD8 cytotoxic responses. Several pathways explained this dichotomy confirmed by nine genes and serum level of CXCL10 were correlated with either TIV-specific cytotoxic CD8+GRZ+ T-cell or antibody responses. A logistic regression analysis demonstrated that these nine genes and serum levels of CXCL10 (D1/D0) best foreseen TIV-specific CD8+GRZ+ T-cell and antibody responses at D21. CONCLUSION: This study provides new insight into the impact of immunization routes and innate signature in the quality of adaptive immune responses.
dc.language.isoENen_US
dc.subject.enSISTM
dc.title.enInnate gene signature distinguishes humoral versus cytotoxic responses to influenza vaccination
dc.title.alternativeJ Clin Investen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/jci125372en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed30843873en_US
bordeaux.journalThe Journal of clinical investigationen_US
bordeaux.page1960-1971en_US
bordeaux.volume129en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamSISTM_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03160706
hal.version1
hal.date.transferred2021-03-06T02:39:09Z
hal.exporttrue
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