Prediction of long-term humoral response induced by the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola

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作者
Marie Alexandre
Mélanie Prague
Chelsea McLean
Viki Bockstal
Macaya Douoguih
Rodolphe Thiébaut
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[1] Inria SISTM,Department of Public Health, Bordeaux University, Inserm UMR 1219 Bordeaux Population Health Research Center
[2] Vaccine Research Institute,Janssen Pharmaceutica N.V.
[3] Janssen Vaccines and Prevention,undefined
[4] Janssen Pharmaceutica N.V.,undefined
[5] Janssen Research and Development,undefined
[6] ExeVir,undefined
[7] Global Commercial Strategy Organization,undefined
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The persistence of the long-term immune response induced by the heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled in six Phase I and Phase II clinical trials conducted by the EBOVAC1 and EBOVAC2 consortia. A model based on ordinary differential equations describing the dynamics of antibodies and short- and long-lived antibody-secreting cells (ASCs) was used to model the humoral response from 7 days after the second vaccination to a follow-up period of 2 years. Using a population-based approach, we first assessed the robustness of the model, which was originally estimated based on Phase I data, against all data. Then we assessed the longevity of the humoral response and identified factors that influence these dynamics. We estimated a half-life of the long-lived ASC of at least 15 years and found an influence of geographic region, sex, and age on the humoral response dynamics, with longer antibody persistence in Europeans and women and higher production of antibodies in younger participants.
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