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Last Updated

07 Aug 2003

Source: Washington Post, August 7, 2003

Scientists Achieve Unexpected Success With Ebola Vaccine

By Justin Gillis, Washington Post Staff Writer

Government scientists have developed a new vaccine against the dread Ebola virus that works rapidly after a single injection, an unexpected success that means the nation could soon have a defense against one of the most fearsome weapons in the terrorist arsenal.

So far the vaccine has been proven to work only in monkeys, which were completely protected against death from Ebola infection when they were exposed to the virus a month after being inoculated. But vaccine results in monkeys usually translate well to humans, and government scientists hope to launch human tests of the vaccine by sometime next year. If all goes well, the vaccine could enter government stockpiles in large quantity as a safeguard against Ebola outbreaks, natural or man-made, as soon as 2006, a decade sooner than many scientists once thought it would take to get an Ebola vaccine.

"In terms of what we need for countermeasures against terrorism, it's highly significant," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which sponsored much of the research. "This could be a real advance in our ability to contain Ebola."

At the same time, the work, to be reported in tomorrow's edition of the journal Nature, raises complex new scientific questions with implications for national security.

The new technique used to create the Ebola vaccine, which involved sophisticated genetic engineering, may be used to create vaccines against other germs, including AIDS and potential terrorist agents. But studies suggest it's possible that any given person could receive a vaccine of this type only once -- subsequent shots might fail to work. That means the government must think carefully about how to use the approach, and about whether to try to maximize its value by, for instance, creating a combination vaccine that would protect against multiple bioterror agents.

Terrifying human outbreaks of Ebola virus have been occurring regularly in Africa, and because the new vaccine works so rapidly, it may well be pressed into service to try to stop one of those epidemics even before the vaccine is formally approved by the Food and Drug Administration.

And eventually, the vaccine could find a highly unusual use in Africa. Ebola is devastating wild populations of gorillas and chimpanzees in parts of the continent, and many scientists have recently realized that the disease, along with a rising illicit trade in ape meat for human consumption, threatens the long-term existence of humankind's closest animal relatives.

Ape biologists universally think a vaccine might be used in captive apes or other special groups to protect them against Ebola, but a few want to go further, vaccinating at least some apes in the wild to try to create barriers to the geographic spread of Ebola virus. The notion raises issues both philosophical and practical issues -- even if it were deemed a good idea, catching thousands of wild gorillas to give them shots would be no mean feat. But if the vaccine continues to hold up in tests, a debate on the issue seems likely.

"It's not a silver bullet," said Peter Walsh, a Princeton University biologist and leading proponent of doing more to save the great apes. At the same time, he said, a vaccination strategy should be considered along with other measures to contain Ebola among apes. "People need to stop being overwhelmed by the difficulties involved in any of these strategies, and start trying to work on them."

Ebola is the virus made famous in Richard Preston's 1995 book, "The Hot Zone." All over the world, some combination of factors -- environmental degradation, human population growth and global trade links have all been cited -- is causing viruses and bacteria to jump from animals to humans and then spread widely, creating new diseases. AIDS is by far the most serious to emerge so far, but Ebola might be the spookiest.

The virus spreads readily from person to person, then kills 90 percent of the people it infects, dissolving internal tissue and sending blood oozing from nearly every orifice of the victim's body. Only two laboratories in the United States, one of them in Frederick, and only a handful in the world have enough safeguards to permit scientists to work on the Ebola virus. Recurring Ebola epidemics in Africa, most recently in the Congo, have killed scores of people at a time, although the disease provokes such alarm that people do whatever is necessary to limit its spread. Many scientists think the United States has escaped a lethal Ebola outbreak only by luck.

In the 1990s, experts realized that Ebola could make a frightening weapon in the hands of terrorists, and their alarm only deepened when they learned that the Soviet Union, in a vast, illegal biowarfare program, had succeeded in creating weapons using Ebola virus. It's still unclear how many people such a weapon could kill, but no one doubts that even a small-scale attack using Ebola virus would set off mass panic. The anthrax attacks of late 2001 created widespread public anxiety even though anthrax does not spread from person to person, treatment is available and those attacks ultimately killed five people.

"Just the word Ebola -- could you imagine how the public would react if there were a couple of cases of Ebola and we know we have no treatment, we have no vaccine, and it's 90 percent fatal?" Fauci said. "That would create panic that I think would make anthrax pale."

Work on an Ebola vaccine goes back years, but only after the 2001 terrorist attacks did serious money start moving into the field. The new vaccine is the product of a successful collaboration between two units of the sometimes-fractious federal health bureaucracy.

The Vaccine Research Center, a unit of Fauci's institute at the National Institutes of Health, in Bethesda, proved three years ago that Ebola vaccination would be possible. But the initial approach was complicated and time-consuming, involving two different types of shots and taking six months or longer to produce immunity. Such a vaccine might be useful to protect health-care workers or soldiers -- it remains under development, in fact -- but it would not be useful to stop an Ebola epidemic.

As NIH worked on a vaccine, the lab in Frederick that works with live Ebola virus, part of the U.S. Army Medical Research Institute of Infectious Diseases, met repeated frustration in its own attempts at vaccine development, creating vaccines that worked in rodents but failed in monkeys, whose biology closely resembles that of humans. At the same time, the Army lab was perfecting an "animal model" the closely resembles human Ebola disease, using macaques, a type of monkey.

The two groups eventually formed a collaboration, and as the scientists were brainstorming, they wondered if one component of the NIH's complicated experimental Ebola vaccine might work as a vaccine all by itself. On a hunch, the scientists decided to test the idea in the macaques.

"We just sort of took a chance," said Peter Jahrling, a top scientist at the Frederick research institute and a leading expert on bioterror agents. "There's lots of naysayers who say you shouldn't be doing studies like that if you don't have data. You know what? We went and did it anyway."

To everyone's surprise, it worked remarkably well. Some monkeys got a single injection of the test vaccine, and some got a fake injection. A month later, they were deliberately infected with Ebola. Those that got the placebo died the usual horrible death, and the ones that got the vaccine didn't get sick at all.

"Lo and behold, the results really exceeded our expectations," said Gary J. Nabel, leader of the NIH vaccine center and principal author of the new Nature paper. "The idea that you could give a single shot and within a month get 100 percent protection, that's clearly encouraging."

Human tests of the first vaccine, the one that requires months of shots, could begin by late this year, while tests of the newer approach could begin in 2004, Nabel said.

The new vaccine does pose some new, and complicated, scientific questions. It was created by genetically manipulating a benign virus called adenovirus to make it look, to the immune system, like Ebola. That causes an immune response that works against subsequent Ebola infection, warding off illness. The approach is theoretically attractive for many types of illness, including other terrorist agents, but it may turn out to have significant limitations.

Some unknown proportion of the population already has natural immunity to adenovirus that could be strong enough to prevent the vaccine from working. Scientists are thinking up ways around that problem, but even if they succeed, a given person might be able to receive an adenovirus vaccine only once, because that first shot would create an immune response that might prevent subsequent adenovirus vaccines from working.

Scientists said the situation could prompt a debate within the government about which adenovirus vaccine should receive the highest priority, or whether to try to create a combination adenovirus vaccine to protect against multiple terrorist agents.