Abstract
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.
Highlights
The unprecedented and rapidly spreading coronavirus disease 2019 (COVID-19) pandemic caused by the emerging coronavirus SARS-CoV-2 calls for swift testing of vaccine candidates prior to initiation of human clinical trials
We found that infection of African green monkeys (AGM) with SARS-CoV-2 resulted in mild disease yet lesions were detectable by positron emission tomography (PET)/computed tomography (CT) imaging of the lungs
This study provides a detailed account of the pathogenesis of a lowpassage SARS-CoV-2 isolate in the AGM model and suggests that AGM can be used for preclinical evaluation of candidate vaccines and therapeutic interventions
Summary
The unprecedented and rapidly spreading coronavirus disease 2019 (COVID-19) pandemic caused by the emerging coronavirus SARS-CoV-2 calls for swift testing of vaccine candidates prior to initiation of human clinical trials. Studies in NHPs are geared towards identifying the most appropriate species that recapitulates human disease. Comprehensive dissection of the longitudinal viral pathogenesis in NHP models is critical for successful evaluation of the efficacy of vaccines, antibody therapeutics, and small molecules in pre-clinical studies. Several NHP models have been reported with SARS-CoV-2 using rhesus and/or cynomolgus macaques and African green monkeys (AGMs) [1,2,3,4]. While used less frequently in biomedical research than rhesus or cynomolgus macaques, AGMs are an old-world NHP species and a natural host for simian immunodeficiency virus (SIV) [5]. This study was designed to understand the pathogenesis of human isolates of SARS-CoV-2 in AGM, including real-time dynamics of virus shedding and whether clinical-grade imaging of NHPs can be used to detect subclinical infections
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