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Development of a Well-Characterized Cynomolgus Macaque Model of Sudan Virus Disease for Support of Product
Kendra J Alfson1, Yenny Goez-Gazi1, Michal Gazi1
1Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78227, USA.
Abstract:
The primary objective of this study was to characterize the disease course in cynomolgus macaques exposed to Sudan virus (SUDV), to determine if infection in this species is an appropriate model for the evaluation of filovirus countermeasures under the FDA Animal Rule. Sudan virus causes Sudan virus disease (SVD), with an average case fatality rate of approximately 50%, and while research is ongoing, presently there are no approved SUDV vaccines or therapies. Well characterized animal models are crucial for further developing and evaluating countermeasures for SUDV. Twenty (20) cynomolgus macaques were exposed intramuscularly to either SUDV or sterile phosphate-buffered saline; 10 SUDV-exposed animals were euthanized on schedule to characterize pathology at defined durations post-exposure and 8 SUDV-exposed animals were not part of the scheduled euthanasia cohort. Survival was assessed, along with clinical observations, body weights, body temperatures, hematology, clinical chemistry, coagulation, viral load (serum and tissues), macroscopic observations, and histopathology. There were statistically significant differences between SUDV-exposed animals and mock-exposed animals for 26 parameters, including telemetry body temperature, clinical chemistry parameters, hematology parameters, activated partial thromboplastin time, serum viremia, and biomarkers that characterize the disease course of SUDV in cynomolgus macaques.
Insights
Cynomolgus macaques infected with Sudan virus (SUDV) exhibit significant physiological changes, establishing them as a viable model for evaluating filovirus disease countermeasures. This research supports the development of SUDV vaccines and therapies.
Area of Science:
- Veterinary Pathology
- Infectious Diseases
- Primate Models
Background:
- Sudan virus (SUDV) causes Sudan virus disease (SVD), a high-fatality illness with no approved treatments.
- Effective countermeasures for SUDV require well-characterized animal models for evaluation.
- Cynomolgus macaques are utilized to model filovirus infections.
Purpose of the Study:
- To characterize the disease progression of SUDV in cynomolgus macaques.
- To assess the suitability of this species as an animal model for evaluating filovirus countermeasures under the FDA Animal Rule.
- To identify key clinical and pathological parameters indicative of SUDV infection.
Main Methods:
- Twenty cynomolgus macaques were inoculated intramuscularly with either SUDV or a control substance.
- Animals were monitored for survival, clinical signs, body weight, and temperature.
- Comprehensive analyses included hematology, clinical chemistry, coagulation, viral load, and histopathology.
Main Results:
- SUDV-exposed macaques showed statistically significant differences in 26 measured parameters compared to controls.
- Key findings included alterations in body temperature, clinical chemistry, hematology, and coagulation.
- Elevated serum viremia and specific biomarkers were identified, characterizing the SUDV disease course.
Conclusions:
- Cynomolgus macaques infected with SUDV provide a relevant model for studying SVD.
- The characterized disease course supports the use of this model for evaluating SUDV countermeasures.
- This study offers valuable data for the development of SUDV vaccines and therapies.
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