The 2014-2016 Ebola outbreak in West Africa has triggered accelerated development of several preventive vaccines against Ebola virus. Under the EBOVAC1 consortium, three phase I studies were carried out to assess safety and immunogenicity of a two-dose heterologous vaccination regimen developed by Janssen Vaccines and Prevention in collaboration with Bavarian Nordic. To describe the immune response induced by the two-dose heterologous vaccine regimen, we propose a mechanistic ODE based model, which takes into account the role of immunological memory. We perform identifiability and sensitivity analysis of the proposed model to establish which kind of biological data are ideally needed in order to accurately estimate parameters, and additionally, which of those are non-identifiable based on the available data. Antibody concentrations data from phase I studies have been used to calibrate the model and show its ability in reproducing the observed antibody dynamics. Together with other factors, the establishment of an effective and reactive immunological memory is of pivotal importance for several prophylactic vaccines. We show that introducing a memory compartment in our calibrated model allows to evaluate the magnitude of the immune response induced by a booster dose and its long-term persistence afterwards.

中文翻译：

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埃博拉病毒疫苗接种后建立、维持和重新激活免疫反应的模型。

2014-2016 年在西非爆发的埃博拉疫情引发了针对埃博拉病毒的几种预防性疫苗的加速开发。在 EBOVAC1 联盟下，进行了三项 I 期研究，以评估由 Janssen Vaccines and Prevention 与 Bavarian Nordic 合作开发的两剂异源疫苗接种方案的安全性和免疫原性。为了描述由两剂异源疫苗方案引起的免疫反应，我们提出了一种基于机械 ODE 的模型，该模型考虑了免疫记忆的作用。我们对所提出的模型进行可识别性和敏感性分析，以确定理想情况下需要哪种生物数据才能准确估计参数，此外，根据可用数据，哪些是不可识别的。来自 I 期研究的抗体浓度数据已用于校准模型并显示其再现观察到的抗体动力学的能力。与其他因素一起，建立有效和反应性的免疫记忆对于几种预防性疫苗至关重要。我们表明，在我们的校准模型中引入记忆隔间可以评估由加强剂量引起的免疫反应的程度及其之后的长期持续性。