Monoclonal antibodies for the treatment of Ebola virus disease

ABSTRACT

Introduction: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies.

Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp™ and MIL-77E cocktails.

Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.

KEYWORDS:

• Ebolavirus disease
• therapy
• monoclonal antibodies
• MB-003
• ZMAb
• ZMapp^TM
• MIL-77E
• mAb114

Article highlights

• The management of patients with suspected or confirmed Ebolavirus disease still depends on quarantine, symptomatic management and supportive care; however, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment by convalescent plasma and monoclonal antibodies.

• To date, around 20 Ebolavirus monoclonal antibodies have been identified and characterized, of which several were found promising to progress to testing in non-human primate models.

• The monoclonal antibodies, which emerged from testing in NHPs as promising for treatment of humans include the single antibody mAb114; the two-mAb cocktail MIL77E and the 3-MAb cocktails MB-003, ZMab and ZMapp^TM.

• The individual mAbs each bind to one of three distinct regions of the Ebolavirus surface glycoprotein; its base, a glycan cap, or a mucin-like domain. MAbs binding to the GP base are neutralizing, whereas antibodies binding the glycan caps or the mucin-like domains appear predominantly non-neutralizing.

• Available data are based on in vitro studies and studies in NHPs, except for ZMAb and ZMapp™: four case reports are available describing compassionate use in humans with EVD. To date, clinical trials on mAb114, MB-003, ZMAb or MIL-77E have not been conducted. A phase I/II clinical trial on ZMapp™ is ongoing.

• Challenges to further develop and to bring mAb therapy to the field are multitude; however, interim advice based on the clinical experience to date is that treatment of Ebola patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.