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

印度恒河猴中亚洲和非洲谱系寨卡病毒的比较发病机制以及适用于评估新药和疫苗的非人类灵长类动物模型的开发

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作者:Jonathan O Rayner, Raj Kalkeri, Scott Goebel, Zhaohui Cai, Brian Green, Shuling Lin, Beth Snyder, Kimberly Hagelin, Kevin B Walters, Fusataka Koide

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.

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