Evaluation of Vaccines and Therapeutics Against Marburg Virus in Nonhuman Primate Models

Marburg virus (MARV) has caused sporadic outbreaks of severe hemorrhagic fever in Africa in humans and nonhuman primates (NHPs) and has the potential to be used as a biological weapon. Currently, there are no licensed vaccines or therapeutics to respond to outbreaks or deliberate misuse. Vaccine and therapeutic efficacy testing against MARV requires animal models that accurately mimic human disease. In vitro testing in cell culture cannot appropriately model the complex immunological host responses required to accurately predict efficacy in humans, which will ultimately be required for licensure of a medical countermeasure (MCM). While small animal models for MARV have been valuable for dissecting disease processes and the screening of vaccine and drug candidates, there are several caveats to their use including required adaptation of the virus, lack of host-specific reagents, or the need of an immunocompromised host. Conversely, the NHP MARV disease model addresses all shortcomings of small animal models and closely recapitulates all hallmark features of human disease. As such, NHPs have served as the "gold standard" for testing filovirus MCMs and will most likely be required for regulatory approval. Here, we describe the use of NHPs for vaccine and therapeutic evaluation against MARV.