» Articles » PMID: 32674252

Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model

Abstract

Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013-2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not.

Citing Articles

Anti-Ebola virus mAb 3A6 protects highly viremic animals from fatal outcome via binding GP in a position elevated from the virion membrane.

Hastie K, Salie Z, Ke Z, Halfmann P, DeWald L, McArdle S Nat Commun. 2025; 16(1):1293.

PMID: 39900911 PMC: 11791206. DOI: 10.1038/s41467-025-56452-2.


Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta).

Wei Y, Li J, Zhu B, Hu Q, Lan M, Zhou J Sci Rep. 2024; 14(1):15677.

PMID: 38977718 PMC: 11231266. DOI: 10.1038/s41598-024-64397-7.


Anti-Ebola virus mAb 3A6 with unprecedented potency protects highly viremic animals from fatal outcome and physically lifts its glycoprotein target from the virion membrane.

Saphire E, Salie Z, Ke Z, Halfmann P, DeWald L, McArdle S Res Sq. 2024; .

PMID: 38196595 PMC: 10775387. DOI: 10.21203/rs.3.rs-3722563/v1.


Natural history of Ebola virus disease in rhesus monkeys shows viral variant emergence dynamics and tissue-specific host responses.

Normandin E, Triana S, Raju S, Lan T, Lagerborg K, Rudy M Cell Genom. 2024; 3(12):100440.

PMID: 38169842 PMC: 10759212. DOI: 10.1016/j.xgen.2023.100440.


Characterization of the Cynomolgus Macaque Model of Marburg Virus Disease and Assessment of Timing for Therapeutic Treatment Testing.

Zumbrun E, Garvey C, Wells J, Lynn G, Van Tongeren S, Steffens J Viruses. 2023; 15(12).

PMID: 38140576 PMC: 10748006. DOI: 10.3390/v15122335.


References
1.
Honko A, Johnson J, Marchand J, Huzella L, Adams R, Oberlander N . High dose sertraline monotherapy fails to protect rhesus macaques from lethal challenge with Ebola virus Makona. Sci Rep. 2017; 7(1):5886. PMC: 5517626. DOI: 10.1038/s41598-017-06179-y. View

2.
Chan M, Leung A, Griffin B, Vendramelli R, Tailor N, Tierney K . Generation and Characterization of a Mouse-Adapted Makona Variant of Ebola Virus. Viruses. 2019; 11(11). PMC: 6893688. DOI: 10.3390/v11110987. View

3.
Pettitt J, Higgs E, Fallah M, Nason M, Stavale E, Marchand J . Assessment and Optimization of the GeneXpert Diagnostic Platform for Detection of Ebola Virus RNA in Seminal Fluid. J Infect Dis. 2016; 215(4):547-553. PMC: 6075475. DOI: 10.1093/infdis/jiw599. View

4.
Bird B, Spengler J, Chakrabarti A, Khristova M, Sealy T, Coleman-McCray J . Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease. J Infect Dis. 2015; 213(5):703-11. PMC: 4747627. DOI: 10.1093/infdis/jiv538. View

5.
Wong G, Leung A, He S, Cao W, de La Vega M, Griffin B . The Makona Variant of Ebola Virus Is Highly Lethal to Immunocompromised Mice and Immunocompetent Ferrets. J Infect Dis. 2018; 218(suppl_5):S466-S470. PMC: 6249576. DOI: 10.1093/infdis/jiy141. View