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针对多种疫苗平台和病原体的疫苗诱导抗体动力学的共识数学模型。

A consensus mathematical model of vaccine-induced antibody dynamics for multiple vaccine platforms and pathogens.

作者信息

Wilding Kristen M, Molina-París Carmen, Kubicek-Sutherland Jessica Z, McMahon Benjamin, Perelson Alan S, Ribeiro Ruy M

机构信息

Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM, United States.

Physical Chemistry and Applied Spectroscopy Group, Los Alamos National Laboratory, Los Alamos, NM, United States.

出版信息

Front Immunol. 2025 Jun 26;16:1596518. doi: 10.3389/fimmu.2025.1596518. eCollection 2025.

Abstract

INTRODUCTION

Vaccine platforms used in successful, licensed vaccines have varied among pathogens. However, antibody level is still the main clinical correlate of protection in most approved vaccines. Decisions as to the best vaccine platform to pursue for a given pathogen may be informed through improved understanding of the process of antibody generation and its temporal dynamics, as well as the relationship between these processes and the type of vaccine.

METHODS

We have analyzed the dynamics of antibody generation for different vaccine platforms against diverse pathogens, and developed a consensus mathematical model that captures antibody dynamics across these diverse systems. Initially, the model was fitted to a rich dataset of antibody and immune cell concentrations in a SARS-CoV-2 vaccine experiment. We then used concepts from machine learning, such as transfer learning, to apply the same model to a variety of systems, involving different pathogens, vaccine platforms, and booster dose use/timing, fixing most parameter values relating to the dynamics of the immune system.

RESULTS

The model includes B cell proliferation and differentiation, as well as the generation of plasma cells, which secrete large amounts of antibody, and memory B cells. Overall, the model describes antibody generation in all systems tested well and shows that the main differences across platforms are related to the dynamics of antigen presentation.

DISCUSSION

This model can be used to predict antibody generation in pairs of vaccine platform/pathogen, allowing for the use of in silico results to narrow down experimental burden in vaccine development.

摘要

引言

成功获批的疫苗所采用的疫苗平台因病原体而异。然而,在大多数获批疫苗中,抗体水平仍是保护作用的主要临床关联指标。通过更好地理解抗体产生过程及其时间动态变化,以及这些过程与疫苗类型之间的关系,可为针对特定病原体选择最佳疫苗平台提供参考依据。

方法

我们分析了针对不同病原体的不同疫苗平台的抗体产生动态,并开发了一个通用数学模型,该模型能够捕捉这些不同系统中的抗体动态。最初,该模型被拟合到一项新冠病毒疫苗实验中丰富的抗体和免疫细胞浓度数据集上。然后,我们运用机器学习中的概念,如迁移学习,将同一模型应用于各种系统,这些系统涉及不同的病原体、疫苗平台以及加强针的使用/接种时间,同时固定了与免疫系统动态相关的大多数参数值。

结果

该模型涵盖了B细胞的增殖与分化,以及分泌大量抗体的浆细胞和记忆B细胞的产生。总体而言,该模型对所有测试系统中的抗体产生情况都描述得很好,并表明不同平台之间的主要差异与抗原呈递的动态变化有关。

讨论

此模型可用于预测疫苗平台/病原体组合中的抗体产生情况,从而利用计算机模拟结果减轻疫苗研发中的实验负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/601f/12241011/91e1f1769e6c/fimmu-16-1596518-g001.jpg

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