An update on nonhuman primate usage for drug and vaccine evaluation against filoviruses.

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Discovery Pub Date : 2024-10-01 Epub Date: 2024-08-18 DOI:10.1080/17460441.2024.2386100
Marc-Antoine de La Vega, Ara Xiii, Shane Massey, Jessica R Spengler, Gary P Kobinger, Courtney Woolsey
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Abstract

Introduction: Due to their faithful recapitulation of human disease, nonhuman primates (NHPs) are considered the gold standard for evaluating drugs against Ebolavirus and other filoviruses. The long-term goal is to reduce the reliance on NHPs with more ethical alternatives. In silico simulations and organoid models have the potential to revolutionize drug testing by providing accurate, human-based systems that mimic disease processes and drug responses without the ethical concerns associated with animal testing. However, as these emerging technologies are still in their developmental infancy, NHP models are presently needed for late-stage evaluation of filovirus vaccines and drugs, as they provide critical insights into the efficacy and safety of new medical countermeasures.

Areas covered: In this review, the authors introduce available NHP models and examine the existing literature on drug discovery for all medically significant filoviruses in corresponding models.

Expert opinion: A deliberate shift toward animal-free models is desired to align with the 3Rs of animal research. In the short term, the use of NHP models can be refined and reduced by enhancing replicability and publishing negative data. Replacement involves a gradual transition, beginning with the selection and optimization of better small animal models; advancing organoid systems, and using in silico models to accurately predict immunological outcomes.

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非人灵长类动物用于丝状病毒药物和疫苗评估的最新情况。
导言:非人类拟态动物(NHP)忠实地再现了人类疾病,因此被认为是评估抗埃博拉病毒和其他丝状病毒药物的黄金标准。长期目标是用更合乎道德的替代品来减少对非人原型的依赖。硅学模拟和类器官模型具有彻底改变药物测试的潜力,因为它们提供了准确的、以人为基础的系统,可以模拟疾病过程和药物反应,而无需考虑与动物试验相关的伦理问题。然而,由于这些新兴技术仍处于发展的初级阶段,目前需要用 NHP 模型来进行丝状病毒疫苗和药物的后期评估,因为它们能为新型医疗对策的有效性和安全性提供重要的见解:在这篇综述中,作者介绍了现有的 NHP 模型,并审查了在相应模型中发现所有具有重要医学意义的丝状病毒药物的现有文献:专家观点:为了符合动物研究的 3R 原则,我们需要有意识地向无动物模型转变。在短期内,可以通过提高可重复性和公布阴性数据来改进和减少非活体动物模型的使用。取而代之的是逐步过渡,从选择和优化更好的小动物模型开始;推进类器官系统的发展,并使用硅学模型来准确预测免疫学结果。
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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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