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亚洲和非洲谱系寨卡病毒在印度恒河猴中的比较发病机制及适合新药和疫苗评估的非人类灵长类动物模型的建立。

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque's and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines.

机构信息

Department of Infectious Disease Research, Southern Research Institute, Birmingham, AL 35205, USA.

Department of Microbiology and Immunology, University of South Alabama, Mobile, AL 36688, USA.

出版信息

Viruses. 2018 May 1;10(5):229. doi: 10.3390/v10050229.

Abstract

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

摘要

建立一个特征良好的 Zika 病毒(ZIKV)感染的非人类灵长类动物模型对于医疗干预措施的发展至关重要。在这项研究中,用 ZIKV 亚洲谱系株对印度恒河猴(IRMs)进行攻毒,导致感染后第 2 至 5 天病毒载量呈剂量依赖性峰值,并产生强大的免疫反应,使动物免受同源和异源再攻毒。相比之下,用非洲谱系株攻毒的 IRMs 的病毒血症低于检测下限,且免疫反应不足以防止再攻毒。这些结果与之前的观察结果一致,但与使用其他非洲株的报告相反,因此无需进一步研究阐明导致差异的因素。尽管如此,用福尔马林灭活的参考疫苗对动物进行免疫接种,并证明对随后的皮下攻毒具有绝育免疫力,验证了亚洲谱系 ZIKV IRM 模型在对策开发中的实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d5f/5977222/f1cb9381d053/viruses-10-00229-g001.jpg

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