Galveston National Laboratory, Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Expert Opin Drug Discov. 2024 Oct;19(10):1185-1211. doi: 10.1080/17460441.2024.2386100. Epub 2024 Aug 18.
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. 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.
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.
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 models to accurately predict immunological outcomes.
由于非人类灵长类动物(NHPs)能够忠实地再现人类疾病,因此它们被认为是评估埃博拉病毒和其他丝状病毒药物的金标准。长期目标是减少对 NHP 的依赖,用更符合伦理的替代方案取而代之。模拟和类器官模型有可能通过提供准确的、基于人类的系统来彻底改变药物测试,这些系统可以模拟疾病过程和药物反应,而不会涉及与动物测试相关的伦理问题。然而,由于这些新兴技术仍处于发展的初期阶段,目前仍需要 NHP 模型来对丝状病毒疫苗和药物进行后期评估,因为它们为新的医疗对策的疗效和安全性提供了重要的见解。
在这篇综述中,作者介绍了现有的 NHP 模型,并研究了相应模型中所有具有医学意义的丝状病毒的药物发现的现有文献。
为了符合动物研究的 3R 原则,我们希望有意识地转向无动物模型。在短期内,可以通过提高可重复性和发表阴性数据来改进和减少 NHP 模型的使用。替代涉及逐步过渡,首先是选择和优化更好的小动物模型;推进类器官系统,并使用模型来准确预测免疫结果。