title: Animal models for ebolavirus countermeasures discovery: what defines a useful model?
abstract: BACKGROUND
  Ebolaviruses are highly pathogenic filoviruses, which cause disease in humans and nonhuman primates (NHP) in Africa. The Zaire ebolavirus outbreak in 2014, which continues to greatly affect Western Africa and other countries to which the hemorrhagic fever was exported due to travel of unsymptomatic yet infected individuals, was complicated by the lack of available licensed vaccines or therapeutics to combat infection. After almost a year of research at an increased pace to find and test vaccines and therapeutics, there is now a deeper understanding of the available disease models for ebolavirus infection. Demonstration of vaccine or therapeutic efficacy in NHP models of ebolavirus infection is crucial to the development and eventual licensure of ebolavirus medical countermeasures, so that safe and effective countermeasures can be accelerated into human clinical trials.
  
  
  METHODS
  The authors describe ebolavirus hemorrhagic fever (EHF) disease in various animal species: mice, guinea pigs, hamsters, pigs and NHP, to include baboons, marmosets, rhesus and cynomolgus macaques, as well as African green monkeys. Because the NHP models are supremely useful for therapeutics and vaccine testing, emphasis is placed on comparison of these models, and their use as gold-standard models of EHF.
  
  
  CONCLUSIONS
  Animal models of EHF varying from rodents to NHP species are currently under evaluation for their reproducibility and utility for modeling infection in humans. Complete development and licensure of therapeutic agents and vaccines will require demonstration that mechanisms conferring protection in NHP models of infection are predictive of protective responses in humans, for a given countermeasure.
authors.affiliation: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Division of Molecular and Translational Sciences , 1425 Porter Street, Frederick, MD 21702 , USA +1 301 619 4246 ; +1 541 754 3545 ; sina.bavari@us.army.mil.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shurtleff
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D046129:Ebola Vaccines / Q000008:administration & dosage; D029043:Ebolavirus / Q000472:pathogenicity*; D019142:Hemorrhagic Fever, Ebola / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D015203:Reproducibility of Results
chemical_list: D046129:Ebola Vaccines
keywords: African green; FDA animal efficacy rule; animal model; antiviral; countermeasure; cynomolgus; ebolavirus; filoviruses; guinea pig; hamster; hemorrhagic fever; in vivo; macaque; marmoset; mice; nonhuman primate; pig; rhesus; therapeutics; vaccine