Antibodies fight Ebola virus in mouse test
By Nathan Seppa
In the 1995 movie Outbreak, an infectious disease of African origin ravages a fictional California town. Easily spread by coughing or sneezing, the ailment causes fever, hemorrhaging, and death among dozens of Hollywood extras. Heroic actors obtain antibodies to the virus from an infected monkey, mass-produce them, inject a patient, and—well, you’ll just have to rent the video.
Despite the melodrama, this plot sounds a lot like an attack of Ebola virus—except for the antibodies. No such treatment is available. Moreover, in patients with the all-too-real virus, antibodies don’t seem to play a major role. Unlike people who’ve bested viral diseases such as smallpox and measles, survivors of Ebola fever don’t have many antibodies against the virus in their blood, and the few they have seem ineffective.
New research, however, suggests that the movie may not be so farfetched. U.S. Army researchers now have evidence that antibodies can thwart Ebola in mice. In the March 3 Science, the scientists describe making five types of antibodies that neutralize a glycoprotein on the surface of Ebola virus-infected cells.
Whether the mice were protected depended in part on the timing of the antibody injections and the amount given. For example, 177 of 200 mice survived when given an antibody either 1 day before or 1 day after infection, but only 52 of 100 survived if given an antibody 2 days after infection. Untreated mice and those receiving antibody 3 days after infection all died.
Researchers adapted a form of Ebola—taken from people who contracted the disease in the Congo, formerly Zaire—to make it lethal to mice. Although the mice were infected only with this Zaire strain of Ebola, test-tube experiments indicate some of the antibodies might also work against strains found in the Ivory Coast and Sudan, says study coauthor Mary Kate Hart, an immunologist at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md.
It isn’t clear how the antibodies protect the mice, Hart says. Each type of antibody binds to a different part of the viral glycoprotein. Binding may keep virus-infected cells from attaching to other cells, she says, and may also incite other immune-system components to spring into action to destroy infected cells.
This work “has shown that antibodies can be protective, in large enough quantities,” says James M. Meegan, a virologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md.
The study also provides “some interesting clues” to which parts of the glycoprotein scientists should concentrate on as they develop neutralizing antibodies, says Anthony Sanchez, a virologist at the Centers for Disease Control and Prevention in Atlanta.
However, Sanchez notes that mice are not as sensitive to Ebola as people or monkeys are. “These are very clear results, but I’m still skeptical as to whether this can be transferred to humans or nonhuman primates,” he says.
Researchers are also trying to create a vaccine against Ebola (SN: 1/10/98, p. 22), but the antibodies might mount a more practical defense, says Yoshihiro Kawaoka, a virologist at the University of Wisconsin—Madison. Ebola outbreaks are sporadic. “Using vaccine may not be the best approach to controlling this disease,” he says. “One has to develop a system with therapeutic approaches. This is one way to do it.”
If there were an Ebola antibody effective in people, it could be rushed to outbreak areas and given to patients and the personnel sent to treat them. Such a drug would also reassure laboratory workers, Meegan says, who currently wear space suit-like gear when handling Ebola.
Hart plans to test the antibodies next in guinea pigs or monkeys.
