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Open AccessArticle

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

1
Disease Intervention and Prevention Program, Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78227, USA
2
Nonclinical Pathology Services, LLC, 3000 Stonebrooke Ln, Medina, OH 44256, USA
3
Battelle Biomedical Research Center (BBRC), 1425 Plain City Georgesville Road, West Jefferson, OH 43162, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current affiliation: Department of Microbiology, National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, 620 Albany St, Boston, MA 02118, USA.
Academic Editor: Andrea Marzi
Microorganisms 2021, 9(3), 489; https://doi.org/10.3390/microorganisms9030489
Received: 29 January 2021 / Revised: 23 February 2021 / Accepted: 23 February 2021 / Published: 26 February 2021
(This article belongs to the Special Issue Hemorrhagic Fever Viruses: Pathogenesis and Countermeasures)
Ebola virus (EBOV) 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. View Full-Text
Keywords: Ebola virus; rhesus macaque; animal model; FDA Animal Rule; natural history Ebola virus; rhesus macaque; animal model; FDA Animal Rule; natural history
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MDPI and ACS Style

Alfson, K.J.; Goez-Gazi, Y.; Gazi, M.; Staples, H.; Mattix, M.; Ticer, A.; Klaffke, B.; Stanfield, K.; Escareno, P.; Keiser, P.; Griffiths, A.; Chou, Y.-L.; Niemuth, N.; Meister, G.T.; Cirimotich, C.M.; Carrion, R., Jr. Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development. Microorganisms 2021, 9, 489. https://doi.org/10.3390/microorganisms9030489

AMA Style

Alfson KJ, Goez-Gazi Y, Gazi M, Staples H, Mattix M, Ticer A, Klaffke B, Stanfield K, Escareno P, Keiser P, Griffiths A, Chou Y-L, Niemuth N, Meister GT, Cirimotich CM, Carrion R Jr.. Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development. Microorganisms. 2021; 9(3):489. https://doi.org/10.3390/microorganisms9030489

Chicago/Turabian Style

Alfson, Kendra J.; Goez-Gazi, Yenny; Gazi, Michal; Staples, Hilary; Mattix, Marc; Ticer, Anysha; Klaffke, Benjamin; Stanfield, Kaylee; Escareno, Priscilla; Keiser, Patrick; Griffiths, Anthony; Chou, Ying-Liang; Niemuth, Nancy; Meister, Gabe T.; Cirimotich, Chris M.; Carrion, Ricardo, Jr. 2021. "Development of a Well-Characterized Rhesus Macaque Model of Ebola Virus Disease for Support of Product Development" Microorganisms 9, no. 3: 489. https://doi.org/10.3390/microorganisms9030489

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