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两剂异源Ad26.ZEBOV、MVA-BN-Filo疫苗诱导的针对埃博拉病毒的长期体液反应预测

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

作者信息

Alexandre Marie, Prague Mélanie, McLean Chelsea, Bockstal Viki, Douoguih Macaya, Thiébaut Rodolphe

机构信息

Department of Public Health, Bordeaux University, Inserm UMR 1219 Bordeaux Population Health Research Center, Inria SISTM, Bordeaux, France.

Vaccine Research Institute, Créteil, France.

出版信息

NPJ Vaccines. 2023 Nov 8;8(1):174. doi: 10.1038/s41541-023-00767-y.

Abstract

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.

摘要

在多项临床试验中,对异源Ad26.ZEBOV、MVA-BN-Filo两剂疫苗接种方案诱导的针对埃博拉的长期免疫反应的持续性进行了研究。分析了参与由EBOVAC1和EBOVAC2联盟开展的六项I期和II期临床试验的487名参与者的IgG结合抗体浓度的纵向数据。使用基于常微分方程的模型来描述抗体以及短期和长期存活的抗体分泌细胞(ASC)的动态变化,以模拟第二次接种疫苗后7天至2年随访期的体液反应。采用基于人群的方法,我们首先评估了最初基于I期数据估计的模型对所有数据的稳健性。然后,我们评估了体液反应的持久性,并确定了影响这些动态变化的因素。我们估计长期存活的ASC的半衰期至少为15年,并发现地理区域、性别和年龄对体液反应动态有影响,欧洲人和女性的抗体持久性更长,年轻参与者产生的抗体更多。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c73/10632397/19d4e1e439bd/41541_2023_767_Fig1_HTML.jpg

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