Dynamics of the humoral immune response to a prime-boost Ebola vaccine: quantification and sources of variation
| dc.rights.license | open | en_US |
| hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | PASIN, Chloe | |
| hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | BALELLI, Irene | |
| dc.contributor.author | VAN EFFELTERRE, T. | |
| dc.contributor.author | BOCKSTAL, V. | |
| dc.contributor.author | SOLFOROSI, L. | |
| hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | PRAGUE, Melanie | |
| dc.contributor.author | DOUOGUIH, M. | |
| hal.structure.identifier | Statistics In System biology and Translational Medicine [SISTM] | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| dc.contributor.author | THIEBAUT, Rodolphe | |
| dc.date.accessioned | 2020-07-09T08:22:09Z | |
| dc.date.available | 2020-07-09T08:22:09Z | |
| dc.date.issued | 2019-09-15 | |
| dc.identifier.issn | 1098-5514 (Electronic) 0022-538X (Linking) | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/10247 | |
| dc.description.abstractEn | The 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.iso | EN | en_US |
| dc.rights | Attribution 3.0 United States | |
| dc.rights.uri | https://creativecommons.org/licenses/by/3.0/us/ | |
| dc.subject.en | SISTM | |
| dc.title.en | Dynamics of the humoral immune response to a prime-boost Ebola vaccine: quantification and sources of variation | |
| dc.title.alternative | J Virol | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1128/jvi.00579-19 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Santé publique et épidémiologie | en_US |
| dc.identifier.pubmed | 31243126 | en_US |
| bordeaux.journal | Journal of Virology | en_US |
| bordeaux.volume | 93 | en_US |
| bordeaux.hal.laboratories | Bordeaux Population Health Research Center (BPH) - U1219 | en_US |
| bordeaux.issue | 18 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.team | SISTM_BPH | |
| bordeaux.team | HEALTHY_BPH | |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03161042 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-03-05T15:33:43Z | |
| hal.export | true | |
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