ZMapp, a New Drug Treatment for Ebola Virus Disease

Ebola virus can cause severe and fatal disease in humans and nonhuman primates such as monkeys or the great apes of Africa. Early estimations suggested that the mortality rate (death rate) from this infection was about 90%, but recent findings suggest that the rate is about 60%, which is still very high. Ebola virus can replicate rapidly in humans and debilitate them quickly (causing symptoms such as fever, hemorrhage, difficulty breathing) so that they cannot effectively produce an immune response that will slow or stop Ebola-caused damage to the body; consequently, there is a race between the body's response and viral (Ebola) replication that Ebola wins in about 60% of infected patients.

There has been an outbreak of Ebola infections in western Africa, where over 700 people have died from Ebola since 2014. Two U.S. missionaries tending to the sick became infected; the missionary group and the infected patients volunteered to use an experimental drug, untried in any humans, in an attempt to save the missionaries, a doctor and an aid worker. The new drug given to them is uniquely designed to allow the human body to win against Ebola replication.

This new drug, termed ZMapp, was developed by a biotech firm (Mapp Biopharmaceutical, Inc.). Several years ago, this company and the National Institutes of Health and the Defense Threat Reduction Agency were tasked to develop a treatment for Ebola virus infection. The drug consists of an anti-Ebola monoclonal antibody cocktail that is made up of three-part mouse and part human antibodies. The mouse part of the antibody is produced in mice immunized against Ebola virus. The active section of the mouse antibody against Ebola was then placed on the human antibody that was modified to carry the part of the mouse antibody that is effective in limiting or stopping Ebola replication.

These chimeric antibodies (one antibody type produced from two different antibodies) were reproduced in Chinese hamster ovary cells and in plant cells that were genetically modified to produce large amounts of chimeric antibodies. These antibodies were then purified and concentrated. In a small study with rhesus macaque monkeys, these antibodies were shown to protect the monkeys from early Ebola virus exposure. They were also successful in reducing or eliminating Ebola viral symptoms in monkeys with ongoing Ebola infection.

However, this drug is still considered experimental because there have been no human clinical trials that provided adequate safety or efficacy data for this drug. A trial in 71 patients in Guinea, Sierra Leon, Liberia, and the U.S. failed to conclusively demonstrate efficacy, although the small numbers did suggest benefit. Because the infected missionary workers (Dr. Kent Brantly and also his infected associate, Nancy Writebol) were apparently losing the battle against Ebola, permission was given to try to save these two with the experimental drug. The drug was effective in slowing or stopping severe symptoms of Ebola within a few hours after administration. To date, it is unknown if all the Ebola virus population in the patients will be eliminated; the two patients will be intensively studied for some time. Unfortunately, this drug is not been produced yet in large quantities; the company reports only a very few doses that could be used in patients. However, the company is trying to increase production.

It is unclear at this point if this drug will become more available to those people who have ongoing Ebola virus infections. In addition, there is some concern that the drug, because it has not been tested for safety or efficacy in any large trial, may not be usable in large populations. In addition, it should be clear that this chimeric antibody is a treatment for ongoing Ebola virus infections; it is not a vaccine. However, there are other investigators attempting to develop an effective vaccine.

Although administration of ZMapp may prevent a person from getting Ebola symptoms, this would be an assumption and has never been tested in humans. It may be possible that the drug may clear an individual of Ebola virus, but the patient may not be immune to other infections with the same virus. More study of this drug is needed. Nonetheless, this is an important step in drug development for the control of devastating viral infections, and we are likely to hear much more about this and similar drugs in the future.