Interrupting Ebola

The 2014 Ebola outbreak is the largest in the disease's history and the first in West Africa, where it has reached multiple countries. Although an approved therapy looks far away, five of seven patients given an experimental combination of mAbs are still alive. But that therapy is only one of several in development, and it is all hands on deck now to push the programs into the clinic.

The ZMapp antibody cocktail from Mapp Biopharmaceutical Inc. is a composite of different mAbs that Mapp, Defyrus Inc., the Public Health Agency of Canada and the University of Manitoba have been working on for at least two years.

The pipeline also contains vaccines and oligonucleotides against Ebola and its close relative, Marburg virus (see "Filovirus pipeline"). Researchers polled by SciBX said that the different approaches should be pursued in parallel given the severity and urgency of the outbreak.

"There is a place for all of these different strategies, such as siRNAs, mAb cocktails and vaccines," said Erica Ollmann Saphire. "Different options might be used at different times."

Ollmann Saphire is a professor of immunology and microbial science at The Scripps Research Institute and director of the Viral Hemorrhagic Fever Immunotherapeutic Consortium.

She said that a vaccine, which would generally be used before exposure to the virus, could be given to aid workers, scientists and people living in or near an outbreak. Antibody and siRNA-based therapies would generally be used post-exposure, although pre-exposure antibodies or post-exposure high-dose vaccines might also work.

Now, each of the modalities has received support from three independent studies that showed specific antibodies, vaccines or siRNAs can prevent or treat disease in nonhuman primates.1-3

ZMapp cocktail

ZMapp is being developed as a therapeutic for infected individuals, and although it has been used in a small number of patients on a compassionate use basis, it still has safety hurdles to satisfy in controlled clinical trials.

The cocktail contains two components from the ZMAb antibody mix provided by a team from the Public Health Agency of Canada and University of Manitoba, and one MB-003 component provided by Mapp. The MB-003 mix contained three human or human-mouse chimeric mAbs, whereas ZMAb was a combination of three mouse mAbs targeting Ebola glycoproteins.

In previous work, the Canadian team showed that ZMAb was partially protective in nonhuman primates when given after fever and virus in the

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