Positive results in monkeys from first ZMapp trial to treat Ebola
An experimental treatment that has already been used in three people has shown 100% protection in non-human primates, reveals a new study.
Source: Patrick Wallet / Look at Sciences / Science Photo Library
ZMapp, an experimental combination of three monoclonal antibodies, has successfully cleared Ebola virus infection in monkeys, paving the way for human trials of the therapy.
The treatment offered 100% protection against Ebola when given up to five days after infection, exceeding the efficacy of any other therapy used in the disease.
“We hope that initial testing in humans will be undertaken soon, preferably within the next few months, to enable the compassionate use of ZMapp as soon as possible,” say the study authors, led by Gary Kobinger, from the Public Health Agency of Canada, Winnipeg, writing in Nature (online, 29 August 2014).
Current approaches to Ebola virus disease are limited to palliative care and barrier methods to prevent transmission. Meanwhile, the latest outbreak is worsening, with 3,069 cases and 1,552 deaths as of 26 August 2014.
In the study, Dr Kobinger and colleagues tested different combinations of chimaeric monoclonal antibodies in guinea pigs and nonhuman primates, and discovered that the optimal formulation contained two antibodies from a previously reported blend and a third from a different combination.
The resultant therapy, ZMapp, was then given to macaque monkeys who had received a lethal dose of Ebola virus. Animals received three doses of ZMapp, given three days apart, starting three, four or five days post-infection. All 18 monkeys treated with ZMapp survived, while the three monkeys given a control substance died within eight days of infection.
ZMapp treatment reversed symptoms of severe Ebola virus disease, such as excessive bleeding, rashes and elevated liver enzymes. ZMapp also reduced the high viral loads in two animals to undetectable levels by day 14.
This study used the “Kikwit” strain of the Ebola virus strain rather than the “Guinean” variant responsible for the West African outbreak. However, by comparing the amino acid sequences of the two variants and undertaking in vitro assays, Dr Kobinger and colleagues say they believe that ZMapp would be similarly effective against the Guinean strain.
ZMapp has already been given to two American healthcare workers infected in the current West African Ebola outbreak, with apparently positive results. It is now being administered to UK citizen William Pooley, who is being treated in the high level isolation unit at the Royal Free Hospital in London after being flown home from Sierra Leone where he contracted the virus while working as a nurse.
The development of ZMapp is described as a “monumental achievement” in an accompanying article by Thomas Geisbert, from the University of Texas, Galveston.
“Although ZMapp in particular has been administered for compassionate use, the next crucial step will be to formally assess its safety and effectiveness,” he writes.
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2014.20066303
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