Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development

• Main Authors: Kendra J. Alfson, Yenny Goez-Gazi, Michal Gazi, Hilary Staples, Marc Mattix, Anysha Ticer, Benjamin Klaffke, Kaylee Stanfield, Priscilla Escareno, Patrick Keiser, Anthony Griffiths, Ying-Liang Chou, Nancy Niemuth, Gabe T. Meister, Chris M. Cirimotich, Ricardo Carrion
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Microorganisms
• Subjects: Ebola virus; rhesus macaque; animal model; FDA Animal Rule; natural history
• Online Access: https://www.mdpi.com/2076-2607/9/3/489

Ebola virus (EBOV)<i> </i>is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger-to-treat” for use in therapeutic studies.