Disease modeling for Ebola and Marburg viruses

Abstract

The filoviruses Ebola and Marburg are zoonotic agents that are classified as both biosafety level 4 and category A list pathogens. These viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in Central Africa. Their natural reservoir has not been definitely identified, but certain species of African bat have been associated with Ebola and Marburg infections. Currently, there are no licensed options available for either treatment or prophylaxis. Different animal models have been developed for filoviruses including mouse, guinea pig and nonhuman primates. The ‘gold standard’ animal models for pathogenesis, treatment and vaccine studies are rhesus and cynomolgus macaques. This article provides a brief overview of the clinical picture and the pathology/pathogenesis of human filovirus infections. The current animal model options are discussed and compared with regard to their value in different applications. In general, the small animal models, in particular the mouse, are the most feasible for high biocontainment facilities and they offer the most options for research owing to the greater availability of immunologic and genetic tools. However, their mimicry of the human diseases as well as their predictive value for therapeutic efficacy in primates is limited, thereby making them, at best, valuable initial screening tools for pathophysiology, treatment and vaccine studies.

Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques

“…The rhesus macaque model was chosen because symptom onset more closely parallels human disease progression compared with the cynomolgus model (27). This proof-of-concept study presents data demonstrating that the plant-produced MB-003 RAMP is efficacious in preventing lethal disease in EBOV-infected macaques when administered 24 or 48 h after virus challenge.…”

Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates

“…Currently, Old World macaques, notably cynomolgus and rhesus macaques, are the gold standard animal model for studying ZEBOV pathogenesis and testing vaccines and therapeutics. Both macaque species are highly susceptible to ZEBOV, with development of viral hemorrhagic fever and 100% lethality (3).…”

A bioluminescent imaging mouse model for Marburg virus based on a pseudovirus system

“…Non-human primates and rodents are the most commonly used animal models for MARV. 19,20 Non-human primates are the most reliable model because the clinical symptoms and pathophysiology are quite similar to those observed in humans. 21 However, the cost and time associated with model are prohibitive for the high-throughput screening of drugs and the early evaluation of vaccines.…”