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一种经质量验证的黄热病疫苗免疫反应的数学计算模型。

A qualitatively validated mathematical-computational model of the immune response to the yellow fever vaccine.

机构信息

Graduate Program in Computational Modeling, Federal University of Juiz de Fora, Juiz de Fora, 36036-900, Brazil.

Presidente Antônio Carlos University - Medical School, Juiz de Fora, 36047-362, Brazil.

出版信息

BMC Immunol. 2018 May 25;19(1):15. doi: 10.1186/s12865-018-0252-1.

Abstract

BACKGROUND

Although a safe and effective yellow fever vaccine was developed more than 80 years ago, several issues regarding its use remain unclear. For example, what is the minimum dose that can provide immunity against the disease? A useful tool that can help researchers answer this and other related questions is a computational simulator that implements a mathematical model describing the human immune response to vaccination against yellow fever.

METHODS

This work uses a system of ten ordinary differential equations to represent a few important populations in the response process generated by the body after vaccination. The main populations include viruses, APCs, CD8+ T cells, short-lived and long-lived plasma cells, B cells and antibodies.

RESULTS

In order to qualitatively validate our model, four experiments were carried out, and their computational results were compared to experimental data obtained from the literature. The four experiments were: a) simulation of a scenario in which an individual was vaccinated against yellow fever for the first time; b) simulation of a booster dose ten years after the first dose; c) simulation of the immune response to the yellow fever vaccine in individuals with different levels of naïve CD8+ T cells; and d) simulation of the immune response to distinct doses of the yellow fever vaccine.

CONCLUSIONS

This work shows that the simulator was able to qualitatively reproduce some of the experimental results reported in the literature, such as the amount of antibodies and viremia throughout time, as well as to reproduce other behaviors of the immune response reported in the literature, such as those that occur after a booster dose of the vaccine.

摘要

背景

尽管 80 多年前就开发出了一种安全有效的黄热病疫苗,但关于其使用仍存在一些不清楚的问题。例如,能够提供针对该疾病免疫力的最小剂量是多少?一种有用的工具,可以帮助研究人员回答这个问题和其他相关问题,即实施描述人体对黄热病疫苗接种免疫反应的数学模型的计算模拟器。

方法

这项工作使用了一个由十个常微分方程组成的系统来表示接种疫苗后身体产生的反应过程中的几个重要群体。主要群体包括病毒、APC、CD8+T 细胞、寿命短的和寿命长的浆细胞、B 细胞和抗体。

结果

为了定性验证我们的模型,进行了四项实验,并将其计算结果与从文献中获得的实验数据进行了比较。这四项实验是:a)模拟个体首次接种黄热病疫苗的情况;b)首次接种后 10 年进行加强剂量的模拟;c)模拟不同初始 CD8+T 细胞水平的个体对黄热病疫苗的免疫反应;d)模拟不同剂量的黄热病疫苗的免疫反应。

结论

这项工作表明,模拟器能够定性再现文献中报道的一些实验结果,例如抗体和病毒血症的数量随时间的变化,以及再现文献中报道的其他免疫反应行为,例如接种疫苗加强剂量后的行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3df/5970533/0ac7494da975/12865_2018_252_Fig1_HTML.jpg

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