Trends in Microbiology
ReviewPost-exposure therapy of filovirus infections
Section snippets
Filovirus infections
Ebola virus and Marburg virus are filamentous, enveloped viruses from the family Filoviridae, which also includes the newly discovered Lloviu virus (LLOV) [1]. It is unknown whether LLOV can cause disease in humans because infectious virions have not yet been isolated [2]. Ebola virus and Marburg virus, in contrast, cause severe disease in humans characterized by the sudden appearance of flu-like symptoms including high fever, severe headache, and myalgia, followed by gastrointestinal symptoms
Post-exposure drugs and vaccines against filovirus disease in NHPs
Candidate treatments are tested for protection in the rhesus (Macaca mulatta) or cynomolgus macaque (Macaca fascicularis) animal models prior to clinical trials. NHPs exhibit many hallmarks observed in human filovirus disease 16, 17 and are considered to be the gold standard animal model available for predicting efficacy in humans. Therapeutic strategies can be grouped into different categories based on their mechanism of action: (i) recombinant nematode anticoagulant protein c2 (rNAPc2) and
Further investigations into the efficacy of mAb therapies
To determine whether mAb therapy can provide any beneficial effects after the progression of EBOV disease, a follow-up study was performed with the MB-003 cocktail. MB-003 was administered to rhesus macaques (n = 7) after two confirmable indicators of disease: (i) detection of viral RNA by reverse transcription-quantitative PCR (RT-qPCR); and (ii) a fever of greater than 1.5°C above the recorded baseline temperature. Dosing of the animals began at the latest 5 days after challenge, and was
Clinical potential and towards a protective pan-filovirus therapy
The number of promising post-exposure treatments for filovirus infections has lagged behind its vaccine counterpart. This is due to the difficulty of rapidly establishing a robust, protective immune response sufficient for combating the virus, and failure to suppress virus replication to manageable levels within an admittedly short timeframe. The primary requirements in the design of a successful candidate treatment include consistently demonstrating the highest levels of protection, offering
Concluding remarks
Monoclonal antibodies are currently the most promising of the available experimental post-exposure options against filovirus infections, as evidenced by the consistently higher rates of survival in lethally challenged NHPs despite a delayed initiation of treatment and fewer doses required for protection. A number of factors will need to be addressed to produce the best possible product (Box 1). From a basic research perspective, the mechanism of action needs to be elucidated for ZMAb and
Disclaimer statement
Her Majesty the Queen in right of Canada holds a patent on the mAbs 1H3, 2G4, and 4G7 (PCT/CA2009/000070), ‘Monoclonal antibodies for Ebola and Marburg viruses.’ The authors declare no other competing interests.
Acknowledgments
This work was supported by the Public Health Agency of Canada (PHAC) and funded by a Canadian Safety and Security Program (CSSP) grant to G.P.K. and X.Q. G.W. is the recipient of a Doctoral Research Award from the Canadian Institute for Health Research (CIHR).
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