Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS Pathog. 2020 Sep 18;16(9):e1008903. doi: 10.1371/journal.ppat.1008903. eCollection 2020 Sep.
Vaccines are urgently needed to combat the global coronavirus disease 2019 (COVID-19) pandemic, and testing of candidate vaccines in an appropriate non-human primate (NHP) model is a critical step in the process. Infection of African green monkeys (AGM) with a low passage human isolate of SARS-CoV-2 by aerosol or mucosal exposure resulted in mild clinical infection with a transient decrease in lung tidal volume. Imaging with human clinical-grade 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) co-registered with computed tomography (CT) revealed pulmonary lesions at 4 days post-infection (dpi) that resolved over time. Infectious virus was shed from both respiratory and gastrointestinal (GI) tracts in all animals in a biphasic manner, first between 2-7 dpi followed by a recrudescence at 14-21 dpi. Viral RNA (vRNA) was found throughout both respiratory and gastrointestinal systems at necropsy with higher levels of vRNA found within the GI tract tissues. All animals seroconverted simultaneously for IgM and IgG, which has also been documented in human COVID-19 cases. Young AGM represent an species to study mild/subclinical COVID-19 disease and with possible insights into live virus shedding. Future vaccine evaluation can be performed in AGM with correlates of efficacy being lung lesions by PET/CT, virus shedding, and tissue viral load.
疫苗是应对全球 2019 年冠状病毒病(COVID-19)大流行的迫切需要,在适当的非人类灵长类动物(NHP)模型中测试候选疫苗是该过程中的关键步骤。通过气溶胶或粘膜暴露用 SARS-CoV-2 的低传代人分离株感染非洲绿猴(AGM)导致轻度临床感染,伴有肺潮气量短暂下降。用人类临床级 18F-氟-2-脱氧-D-葡萄糖正电子发射断层扫描(18F-FDG PET)与计算机断层扫描(CT)共同进行的成像显示,感染后 4 天(dpi)出现肺部病变,随着时间的推移而消退。所有动物均以双相方式从呼吸道和胃肠道(GI)中排出传染性病毒,首先在 2-7dpi 之间,然后在 14-21dpi 时再次复发。在尸检时,在整个呼吸道和胃肠道系统中均发现了病毒 RNA(vRNA),在胃肠道组织中发现了更高水平的 vRNA。所有动物同时针对 IgM 和 IgG 发生血清转化,这在人类 COVID-19 病例中也有记录。年轻的 AGM 代表着研究轻度/亚临床 COVID-19 疾病的物种,并且可能对活病毒脱落有深入了解。未来可以在 AGM 中进行疫苗评估,其疗效相关性为 PET/CT 检测的肺病变、病毒脱落和组织病毒载量。