mRNA疫苗开发与优化的多尺度定量系统药理学模型

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Lorenzo Dasti, Stefano Giampiccolo, Elisa Pettinà, Giada Fiandaca, Natascia Zangani, Lorena Leonardelli, Fabio De Lima Hedayioglu, Elio Campanile, Luca Marchetti
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引用次数: 0

摘要

应对COVID-19大流行的前所未有的努力释放了mRNA疫苗作为一种强大技术的潜力,这种技术将在未来几年变得越来越普遍。与药物开发的其他领域一样,数学建模是支持和加快mRNA疫苗开发过程的关键工具。本研究引入了定量系统药理学(QSP)模型,该模型捕获mRNA疫苗接种后的关键免疫反应,包括组织水平和分子水平的事件。该模型从机制上描述了从抗原呈递细胞在注射部位摄取mRNA到随后将抗体释放到血液中的生物学过程。这种双层模型首次尝试将导致抗原表达的分子机制与免疫反应联系起来,为未来整合特定疫苗属性(如mRNA序列特征和基于纳米技术的递送系统)铺平了道路。该模型专门针对BNT162b2 SARS-CoV-2疫苗进行了校准,已在各种给药方案和给药计划中成功验证。结果强调了该模型在优化剂量策略方面的有效性,并强调了免疫反应的关键差异,特别是在老年人等低反应群体中。此外,该模型的适应性已通过其校准其他mRNA疫苗(如Moderna mRNA-1273疫苗)得到证实,强调了其在mRNA疫苗研究和开发中的通用性和广泛适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Multiscale Quantitative Systems Pharmacology Model for the Development and Optimization of mRNA Vaccines.

The unprecedented effort to cope with the COVID-19 pandemic has unlocked the potential of mRNA vaccines as a powerful technology, set to become increasingly pervasive in the years to come. As in other areas of drug development, mathematical modeling is a pivotal tool to support and expedite the mRNA vaccine development process. This study introduces a Quantitative Systems Pharmacology (QSP) model that captures key immune responses following mRNA vaccine administration, encompassing both tissue-level and molecular-level events. The model mechanistically describes the biological processes from the uptake of mRNA by antigen-presenting cells at the injection site to the subsequent release of antibodies into the bloodstream. This two-layer model represents a first attempt to link the molecular mechanisms leading to antigen expression with the immune response, paving the way for the future integration of specific vaccine attributes, such as mRNA sequence features and nanotechnology-based delivery systems. Calibrated specifically for the BNT162b2 SARS-CoV-2 vaccine, the model has undergone successful validation across various dosing regimens and administration schedules. The results underscore the model's effectiveness in optimizing dosing strategies and highlighting critical differences in immune responses, particularly among low-responder groups such as the elderly. Furthermore, the model's adaptability has been demonstrated through its calibration for other mRNA vaccines, such as the Moderna mRNA-1273 vaccine, emphasizing its versatility and broad applicability in mRNA vaccine research and development.

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来源期刊
CiteScore
5.00
自引率
11.40%
发文量
146
审稿时长
8 weeks
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