Nonhuman primates as models for the discovery and development of ebolavirus therapeutics

Abstract

Introduction: Ebolaviruses are human pathogenic Category A priority pathogens for which no vaccines or therapeutics are currently licensed; however, several therapeutic agents have shown promising efficacy in nonhuman primate models of infection and are potential candidates for use in humans. Demonstration of efficacy in nonhuman primate models of ebolavirus infection will probably be central to the development and eventual licensure of ebolavirus medical countermeasures given the ethical and feasibility constraints of human efficacy assessments.

Areas covered: The authors describe ebolavirus hemorrhagic fever (EHF), with an emphasis on comparing human and nonhuman primate pathophysiology. Published data examining human and animal clinical disease parameters, histopathological findings, and immune responses in fatal and nonfatal cases are synthesized and evaluated. Importantly, the authors also introduce and describe the FDA Animal Efficacy Rule as well as recent advances in antiviral drug development strategies for the treatment of EHF.

Expert opinion: Well-characterized models of ebolavirus infection are currently under development and scrutiny as to their accuracy and utility for modeling fatal infection in humans. The advanced development and eventual licensure of therapeutic agents will require demonstration that mechanisms conferring protection in nonhuman primate models of infection are predictive of protective responses in humans.

Keywords::

• animal model
• antiviral
• cynomolgus
• ebolavirus
• FDA Animal Efficacy rule
• filoviruses
• hemorrhagic fever
• in vivo
• nonhuman primate
• prophylaxis
• rhesus
• therapeutics
• therapy
• treatment

Acknowledgments

The authors thank numerous colleagues and peers who are striving to develop filovirus medical countermeasures and regret that space limitations prevented inclusion of particular articles. Support for filovirus evaluations has been provided by the US Defense Threat Reduction Agency (1.1C003_08_RD_B) and by Transformational Medical Technologies (TMTI0048_09_RD_T). The opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Army.

Notes

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