ZMapp Reverses Ebola Infection in Animal Testing

Although debate has swirled around the impact the experimental drug ZMapp actually had on 2 American relief workers infected with the Ebola virus, a recent study suggests the treatment may have played a significant role in their recovery.

Researchers reported in Nature this week that the use of ZMapp in 18 rhesus macaques resulted in 100% recovery following treatment with the drug, even up to 5 days after infection. ZMapp, which was developed by San Diego-based Mapp Biopharmaceutical, Inc, gained exposure after it was used to treat Americans Dr. Kent Brantly and Nancy Writebol, who showed signs of recovery shortly after receiving the drug.

The pair, who became infected with Ebola while working with patients in Liberia, were released earlier this month from Emory University Hospital after being airlifted to the United States for treatment. However, the role ZMapp played in their recovery is unknown.

"If the question is, 'Did Zmapp do this?' The answer is that we just don't know," Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Disease, told USA Today last week.

Earlier this week, however, the deputy chief medical doctor for Liberia’s largest hospital died of the virus just weeks after receiving 1 of the 6 available doses of ZMapp. The drug was also used to treat 75-year-old Spanish priest Miguel Pajares, who contracted the disease during relief efforts in Liberia. Less than 1 week after he was airlifted to Madrid, Pajares died on August 12, 2014, though officials said that old age may have been a factor.

ZMapp acts as a cocktail of monoclonal antibodies that bind and inactivate the virus by recognizing infected cells and triggering the immune system to kill them off, according to Mapp.

For the study published in Nature, a team of researchers administered 3 doses of ZMapp at 3-day intervals starting on day 3, 4, or 5 after the primates were infected with Ebola. All 18 animals experienced a reversal of severe Ebola virus symptoms, including excessive bleeding, rashes, and elevated liver enzymes, the authors wrote.

Additionally, 3 of the rhesus macaques that did not receive ZMapp all died from the infection by day 8.

The Ebola strain used to infect the monkeys in the study was not the same as the Zaire strain currently impacting West African, but the researchers said they used a direct comparison of the 2 variants of the virus, which suggested that ZMapp could limit replication of the new strain.

The World Health Organization (WHO) said yesterday that the Ebola virus could infect more than 20,000 people in West Africa before the outbreak is brought under control, according to a report in the New York Times. To date, the virus has killed more than 1500 people with just over 3000 confirmed and suspected cases in the countries of Guinea, Liberia, Sierra Leone, and Nigeria, according to the WHO.

With such a dire forecast for the spread of Ebola, research to find a cure has been accelerated on several fronts. In addition to ZMapp, a collaboration on a vaccine by the National Institutes of Health and GlaxoSmithKline is expected to begin human safety trials as early as next week.

Despite the promising results of the study on ZMapp, virologist Thomas W. Geisbert, PhD, wrote in an accompanying commentary that testing the drug in humans might be problematic.

“Although ZMapp, in particular, has been administered for compassionate use, the next crucial step will be to formally assess its safety and effectiveness,” Dr. Geisbert wrote. “Testing the latter is clearly difficult, because intentional infection of human subjects in clinical trials is not possible. US regulations, however, could allow the treatment to be licensed for widespread use on the basis of safety testing in humans and efficacy testing in animals. In the long run, the manufacture of ZMapp could require investment in infra­structure for making monoclonal antibodies at an industrial scale—assuming that funding is available to pay the production costs.”