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Dynamics of the humoral immune response to a prime-boost Ebola vaccine: quantification and sources of variation

dc.rights.licenseopenen_US
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPASIN, Chloe
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBALELLI, Irene
dc.contributor.authorVAN EFFELTERRE, T.
dc.contributor.authorBOCKSTAL, V.
dc.contributor.authorSOLFOROSI, L.
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPRAGUE, Melanie
dc.contributor.authorDOUOGUIH, M.
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
dc.date.accessioned2020-07-09T08:22:09Z
dc.date.available2020-07-09T08:22:09Z
dc.date.issued2019-09-15
dc.identifier.issn1098-5514 (Electronic) 0022-538X (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10247
dc.description.abstractEnThe Ebola vaccine based on Ad26.ZEBOV/MVA-BN-Filo prime-boost regimens is being evaluated in multiple clinical trials. The long-term immune response to the vaccine is unknown, including factors associated with the response and variability around the response. We analyzed data from three phase I trials performed by the EBOVAC1 consortium in four countries - UK, Kenya, Tanzania and Uganda. Participants were randomized in four groups based on the interval between prime and boost immunization (28 or 56 days) and the sequence in which Ad26.ZEBOV and MVA-BN-Filo were administered. Consecutive ELISA measurements of the IgG binding antibody concentrations against the Kikwit glycoprotein (GP) were available in 177 participants to assess the humoral immune response up to 1 year post prime. Using a mathematical model for the dynamics of the humoral response, from 7 days after the boost immunization up to 1 year after the prime immunization, we estimated the durability of the antibody response and the influence of different factors on the dynamics of the humoral response. Ordinary differential equations (ODEs) described the dynamics of antibody response and two populations of antibody-secreting cells (ASC), short-lived (SL) and long-lived (LL). Parameters of the ODEs were estimated using a population approach. We estimated that half of the LL ASCs could persist at least five years. The vaccine regimen significantly affected the SL ASCs and the antibody peak but not the long-term response. The LL ASCs compartment dynamics differed significantly by geographic regions analyzed, with a higher long-term antibody persistence in European subjects. These differences could not be explained by the observed differences in cellular immune response.IMPORTANCE With no available licensed vaccines or therapies, the West African Ebola virus disease epidemic of 2014-2016 caused 11,310 deaths. Following this outbreak, the development of vaccines has been accelerated. Combining different vector-based vaccines as heterologous regimens could induce a durable immune response, assessed through antibody concentrations. Based on data from phase 1 trials in East Africa and Europe, the dynamics of the humoral immune response from 7 days after the boost immunization onwards were modeled to estimate the durability of the response and understand its variability. Antibody production is maintained by a population of long-lived cells. Estimation suggests that half of these cells can persist at least five years in humans. Differences in prime-boost vaccine regimens affect only the short-term immune response. Geographical differences in long-lived cell dynamics were inferred, with higher long-term antibody concentrations induced in European participants.
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.enDynamics of the humoral immune response to a prime-boost Ebola vaccine: quantification and sources of variation
dc.title.alternativeJ Virolen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1128/jvi.00579-19en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31243126en_US
bordeaux.journalJournal of Virologyen_US
bordeaux.volume93en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue18en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamHEALTHY_BPH
bordeaux.teamSISTM_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03161042
hal.version1
hal.date.transferred2021-03-05T15:33:43Z
hal.exporttrue
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