Ebola virus inflicts viral hemorrhagic fever on humans. Despite years of intensive research, there is no preventive vaccine against Ebola virus, and no therapeutic treatment. Its mortality rate skirts 80 percent of people infected.
Ebola virus made the headlines in 1995, when a sudden devastating outbreak exploded in the east African town of Kikwit in Zaire (re-named Democratic Republic of Congo). It infected 315 people, of whom 243 died - including a number of health care workers. The Ebola virus was named for the Ebola River, which flows through the epicentric region of the epidemic. The latest outbreak struck in Uganda during October and November of 2000. It infected 329 victims, of whom 107 died. Right now another outbreak is raging in the Congo Republic, said molecular biologist Gary Nabel, who heads the Vaccine Research Center of the NIAID - NIH's National Institute of Allergy and Infectious Diseases.
Vaccinologists have never given up their research struggle against Ebola virus. Their latest word appears in today's issue of Nature, dated Aug. 7, 2003. The paper's title: "Accelerated vaccination for Ebola virus hemorrhagic fever in non-human primates." Nabel is senior author.
"I think this article's finding," Nabel observed, "is that we've developed a way to respond to Ebola virus outbreaks by a fast-action interventional vaccine candidate. This new vaccine approach," he added, "will allow us to inject a single time for protection against lethal challenge to the vaccinated animals. (See BioWorld Today, Nov. 30, 2000.)
"In previous vaccine studies," he continued, "we used a DNA prime-boost strategy followed by an adenovirus vector. To achieve that infection protection schedule took a longer period of time - eight months from when we started the injections and actually challenged the virus. In an acute outbreak setting, that's not the most efficient vaccine. It's very good for prevention, to vaccinate people at higher risk ahead of time. But in the setting of a natural Ebola virus outbreak, we wanted to find a way to intervene and deliver some of the protection to people more quickly."
Did Former Soviet Union Weaponize Ebola?
"While developing our new vaccine," Nabel went on, "we are still planning to pursue the previous version with the DNA prime boost. And we continue to work with biotech companies on that project. As to this DNA part, we're still in business with Vical Inc. in San Diego, and plan to move that forward into the clinic as well. But this more interventional vaccine, we see as being more appropriate for responding to an acute outbreak or a deliberately planted Ebola virus - more like a bioweapon of mass infection. It's my understanding," Nabel explained, "that Ebola has been reported to be weaponized in the past by the former Soviet Union. Their military had been working on experiments to weaponize both Marburg and Ebola viruses. And that's one reason why Ebola is listed on the Category A list among the viral hemorrhagic fevers.
"In this new vaccine, we took the other component of the previously successful product, namely the adenoviral [AV] vector. With that gene-delivery vehicle the kinetics of the immune response appeared more quickly when we vaccinated with AV alone. It wasn't as strong an immune response as the DNA prime boost and AV together, but it was still reasonably good and quicker. So we investigated whether that degree of immunity was sufficient for protection - the AV alone without the DNA. It was.
"In our new vaccine, delivery of the Ebola antigenic genes was a mixture of three adenoviral vectors. They were crippled, replication-defective, so unable to multiply out of bounds. Each contained one Ebola gene product. That included the glycoprotein from either the Zaire strain or the Sudan strain of Ebola virus plus the viral nuclear protein that virions use to form capsid or envelope."
To groom their newest Ebola vaccine for eventual human field trials, Nabel and his co-authors conducted preclinical tests with mice and cynomolgus macaque monkeys.
"In the monkeys - the animal species we report in the Nature paper," he said, "we tried different AV immunizations and different infectious challenges of the virus. Ultimately, that showed a single AV vaccination protected against either a low- or a high-dose challenge at one month later. Results in the vaccinated animals amounted to complete protection against lethal infection.
"This animal work was done over the past year," Nabel recounted, "with our collaborators at the U.S Army Medical Research Institute of Infectious Diseases [USAMRIID in Fort Detrick, Md.]. First we immunized eight monkeys with a single-boost injection, consisting of attenuated carrier viruses containing genes for important Ebola antigens. We then delivered the eight animals to USAMRIID, where they were injected with an Ebola virus strain obtained from a fatally infected person from the former Zaire outbreak in 1995. The single vaccine injection completely protected all eight animals against Ebola infection, regardless of dose."
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Peter Jahrling, senior research scientist at USAMRIID and the Nature paper co-author, said in a press statement, "I am proud that our research team at USAMRIID was able to form an effective partnership with our colleagues at NIAID to develop and evaluate this new Ebola vaccine."
Nabel said, "The take-home lesson is that this vaccine apparently induces both cellular and humoral immunity.
"We previously found that the level of antibody response seemed to be a good predictor of protection. But the antibody alone is probably not sufficient. It may be CD8 cells are contributing.
"Ebola virus spreads easily from person to person," Nabel said. "It causes illness quickly and kills a significant number of the patients it infects. Ring vaccination might be used to stop its spread during acute outbreaks," he suggested, "just as the ring strategy was used to contain smallpox in the past. With ring vaccination, everyone who has been in contact with a patient, as well as all members of the patient's household, are vaccinated.
"For the AV vector," Nabel reflected, "if all goes well, it's possible that a Phase I vaccine trial could go forward within two years. What for me is encouraging, and an interesting opportunity for the future, is an essentially new way of looking at more intervention than preventive medicine. And the two can work together to intervene in that. We may be nearing the point," he concluded, "where we can use these tools more actively."