Monkeys OK for Six Months The researchers, including members of the Special Pathogens Branch at the Centers for Disease Control in Atlanta, say four vaccinated monkeys were completely protected from a lethal dose of the virus. The animals have been symptom-free with no detectable virus in their blood for six months after they were infected. We have not known if immunity to the virus exists or what parts of the immune response are important, explains Nabel. Our studies show animals can launch an effective response against the Ebola virus and we can use knowledge of this response to design a vaccine that protects nonhuman primates from infection.  Human Studies Soon? Nabel is planning to work with the Food and Drug Administration to begin testing the safety of the vaccine in humans while additional studies continue in primates. The Ebola virus is particularly virulent, killing quickly and giving the body little time to launch an effective immune response. Infected individuals suffer severe pain, high fever and extensive internal bleeding. All doctors can do is provide fluids to restore the lost blood. While the virus periodically strikes humans, scientists do not know where in nature it resides between outbreaks. Although other viral diseases claim more victims each year, the nightmarish symptoms of Ebola make it a key target for scientists. A vaccine, if developed, would probably be offered to family members and contacts of those infected and health-care professionals who first confront the diseased during an outbreak. Field workers and laboratory researchers also could benefit, experts say. Mass immunization in Africa most likely would not occur because of lack of funding and the difficulty of vaccinating communities in remote regions.  First Outbreak in 1976 The virus, a member of the filovirus family, emerged in the African rain forest in 1976. It caused two outbreaks at the time, one in Sudan and one in the northern part of the Democratic Republic of Congo, then called Zaire. Another strain has infected Ivory Coast. The Zaire strain emerged again nearly 20 years later some 600 miles away in the Democratic Republic of Congo. The Sudan strain recently re-emerged to cause an outbreak that is still affecting Uganda, with the death toll at 129 people. Ebola is a difficult virus because currently available antiviral drugs have no proven effect on it and we do not know its natural reservoir [where it resides in nature between outbreaks], making environmental control impossible, says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which funds Nabels research. A vaccine is therefore the best hope for protecting humans from infection and this study makes some key advances toward realizing that goal, Fauci says. Developing a vaccine against Ebola is tricky, explains Paul Parren, assistant professor at the Scripps Research Institute, in La Jolla, Calif., writing an accompanying article in Nature. Parren studies antibodies that neutralize the virus as potential vaccine candidates. A vaccine that consists of killed or attenuated [weakened] virus is unlikely, for safety reasons to be accepted by health bodies or the public, Parren wrote along with colleague Dennis Burton. Moreover, any vaccine must be tested under rigorous Biosafety 4 conditions, which require special facilities and are expensive. Vaccines often use a modified version of the actual disease-causing microbe to provide immunity to healthy people from future infection by the microorganism. But vaccines under development may pose risks to subjects.  Monkeys Got Two Shots Nabels latest study is built on prior research. Earlier studies in Nabels laboratory used a vaccine from a protein in one Ebola virus strain. Technicians injected the vaccine into the muscles of guinea pigs, eliciting an immune response and protecting the animals from a later infection. But a similar vaccine, modified to contain proteins from the three strains of Ebola, did not produce a sufficient immune response when injected into the monkeys, Nabel says. To enhance the immune response in the monkeys, Nabels team also gave them a shot consisting of a weakened adenovirus  or a virus that can cause colds in humans  genetically engineered to contain a protein from the Zaire strain of the virus. Both injections enabled the monkeys to develop a strong immune response. Scientists injected four monkeys with the three-strain Ebola virus vaccine, the adenovirus-Ebola booster and the Zaire strain of the Ebola virus. While three of the monkeys showed no sign of viral infection, one had slightly elevated viral blood levels, which then disappeared after one week. Four monkeys that received a placebo died a week after infection.  Further Testing Against Other Strains The researchers plan to test their method against infection with all three strains of the virus, says Dr. Nancy Sullivan, a research fellow who works with Nabel. The scientists also expect to perform further experiments to understand the mechanism of immune protection offered by the vaccine. While enthusiastic about the findings, Parren said the researchers also should test their vaccine with a higher dosage of virus to mimic real-life conditions. Parren says Nabels group infected the monkeys with approximately 100 to 200 copies [particles] of the Zaire strain of the Ebola virus. But infected people harbor 10,000 times that number of virus in their blood. In response, Nabel says the small level was sufficient to kill those monkeys that did not receive the vaccine. His laboratory plans to study the effect of increasing the dose of the virus as well as beginning the process of testing the vaccine in humans. It is important that we recognize that to develop a vaccine against Ebola, or AIDS or even cancer, we learn a lot by animal models, but it is studies in humans that tell us if it is working, Nabel says.
- Scientists may be one step closer to developing a vaccine for the dreaded Ebola virus, a deadly microbe that periodically attacks African villages and can kill up to 90 percent of the people it infects within a very short time.