When a virus jumps species, it's a bad thing.
Usually, it is more virulent in its new host. The new host has limited or no immunity, precisely because it is not in an ecological balance with its viral predator.
The result? Epidemics.
The most well-known epidemic is the annual flu season, which begins when flu strains from either birds or pigs make their way into the human population.
Ebola and Marburg virus outbreaks are rarer and more limited than influenza, but due to a number of factors, they nevertheless have commanded a lot of attention from the general public. They have starred in a bestseller, Richard Preston's "The Hot Zone," and a Hollywood thriller, "Outbreak," in which Dustin Hoffmann and Rene Russo save the world by developing a counteragent to the mysterious "Motaba" virus, which behaves remarkably like Ebola, in about 24 hours.
But Ebola and Marburg virus also are in the crosshairs of the U.S. military, which considers them Category A bioterrorist hazards and has been working on developing both vaccines and therapeutics.
Of course, in vaccine and therapeutic development, one of the main challenges is developing an agent that will be successful in humans. And as with viruses, what will work in one species is far from a sure thing in another. But in a Nature Medicine paper now available via advance online publication, researchers report that they have developed a vaccine system that protects macaque monkeys against infection with Ebola and Marburg virus - a model system that, while still not quite the real thing, is a much better predictor of success in humans than mice or guinea pigs.
"The main success story here is that we have one vaccine system, the first and only one, that works in non-human primates," Tom Geisbert, chief of viral pathology at U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), told BioWorld Today. "In that sense, we've made more progress in the last three to four years than in the 14 years before that. It's very easy to protect rodents, but for years, we'd get protection in rodents, get really excited, and we'd transition it to nonhuman primates and it wouldn't work."
Geisbert is senior author of the paper, which is a joint effort by scientists from the USAMRIID, the National Institute of Allergy and Infectious Diseases and the Uniformed Services University of the Health Sciences, all located in Bethesda, Md., as well as the National Microbiology Laboratory of the Public Health Agency of Canada; the University of Manitoba in Winnipeg; Philipps University in Marburg, Germany; and the University Claude Bernard in Lyon, France.
The researchers first vaccinated six monkeys each with a surface glycoprotein of either Ebola Zaire, the deadliest strain of Ebola, or Marburg virus engineered into a carrier virus known as vesicular stomatitis virus, or VSV. One advantage of the VSV carrier is that infection with it is rare - but then, so is immunity. Of course, the goal of the vaccine is to develop immunity to Ebola or Marburg virus, not the carrier, but Geisbert explained that "if you have a person that has antibodies against the carrier, they can inactivate the carrier before you can get an immune response to Ebola."
Four weeks after vaccination, the monkeys were injected with either Ebola Zaire or Marburg virus; two animals in each group were cross-challenged, while the other four were challenged with the same virus they had been vaccinated with. Ebola vaccination did not cross-protect monkeys against Marburg virus and vice versa, which was in line with the researchers' expectations. But none of the monkeys that were tested with the same virus they had been vaccinated with developed any clinical symptoms whatsoever.
The researchers also tested whether vaccinating with one strain of Ebola or Marburg virus protected against different strains of the same virus, with mixed results. Geisbert summarized, "Vaccination with Ebola Zaire offers no protection against Ebola Sudan - we know we'll have to include a gene for Sudan. Marburg, we're not sure yet, but it looks like we may be able to get away with only using one strain."
Geisbert is sanguine about the necessity of administering at least three different viral strains, noting that they could either be administered as a combination or even engineered onto the same carrier virus, depending on how strong an immune response each method would elicit.
The vaccine, if successful in clinical trials, would have both bioterrorist and civilian applications. Geisbert specifically mentioned health care and laboratory workers as two groups that he hopes will benefit from a vaccine.
"At USAMRIID, our primary mission is to protect fighters," he said. "But at the same time, we certainly want to help with the humanitarian aspects."