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Intravenous administration (IV) of antiviral monoclonal antibodies (mAbs) is challenging due to limited resources for performing infusions during an ongoing epidemic. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce these burdens and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a two mAb pan-ebolavirus cocktail, reverses the course of Sudan ebolavirus (SUDV/Gulu) disease with a single IV or IM dose in non-human primates (NHPs) as far as five days post-exposure. Furthermore, we investigated the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. MBP431 demonstrated an extended serum half-life in vivo and offered complete or significant protection with a single IM dose delivered as a post-exposure prophylactic (PEP) or therapeutic in NHPs challenged with EBOV. These results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known ebolavirus.

The current Zaire ebolavirus (ZEBOV) epidemic in West Africa reinforces the need for effective vaccines and therapeutics that protect against all species of ebolavirus (EBOV). To achieve this, we characterized the effect of virus infection of macrophages and dendritic cells using the recently discovered Bundibugyo ebolavirus (BEBOV). BEBOV infection of humans and nonhuman primates has a lower case fatality rate, differing clinical presentations, and longer time to death compared to ZEBOV. More importantly, survivors and non-survivors of BEBOV have detectable antibodies against BEBOV, indicating that BEBOV interaction with immune cells may differ from ZEBOV. To better understand BEBOV pathogenicity and determine the effects of BEBOV on macrophages and dendritic cells, we performed growth curves and cell characterization in monocyte-derived dendritic cells and PMA-induced THP-1 macrophage-like cells. Over 96 hours, virus production was measured by virus titer, flow cytometry, and qRT-PCR. During monocyte derived dendritic cell experiments, cell surface markers were characterized over time to determine changes induced by EBOV infection. In all cell types tested, BEBOV grows to a lower viral titer. This may play an important role in the overall pathogenesis of BEBOV. Understanding the systemic immune response to BEBOV will aid in determining the mechanism of decreased pathogenesis and identify antiviral targets to be used in developing broad spectrum EBOV therapeutics.

The first cases of Ebola hemorrhagic fever were reported from Sudan and Zaire (now Democratic Republic of the Congo) in 1976, but the virus has only received significant attention since 1995. Until recently, the development of therapeutics or vaccines was not considered a priority. The knowledge gained during the past decade on the biology and pathogenesis of Ebola virus has led to the development of therapeutic strategies that are currently being investigated. Considering the aggressive nature of Ebola infections, in particular the rapid and overwhelming viral burdens, early diagnosis will play a significant role in determining the success of any intervention strategy. Advanced understanding of the immune response has produced several vaccine candidates of which a few can be considered for further evaluation. This review will summarize and discuss the current therapeutic and prophylactic strategies for Ebola hemorrhagic fever.