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For Ebola researcher, setbacks set stage for vaccine test

Dr. Nancy Sullivan said it was hard to unravel the many mysteries of the immune system to create a vaccine.Cliff Owen/Associated PRess

WASHINGTON — It took 16 years of twists and turns. Again and again, Dr. Nancy Sullivan thought she was close to an Ebola vaccine, only to see the next experiment fail.

“A case of resuscitation more than once” is how the National Institutes of Health researcher describes the journey.

But it is those failures that Sullivan, a native of Wilmington, Mass., credits for finally leading her to a vaccine promising enough to test in parts of West Africa ravaged by Ebola.

Last week, volunteers in Liberia’s capital began rolling up their sleeves for the first large-scale testing of two potential Ebola vaccines, the one Sullivan developed at NIH and a similar one created by Canada’s government.

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Ebola has claimed nearly 9,000 lives in West Africa over the past year, although new infections have dropped dramatically in recent months. It’s too soon to declare victory: Last week, new cases inched up for the first time this year, and health officials fear a resurgence if they don’t completely stamp out the disease before the upcoming rainy season.

Waning cases make it more difficult to tell if a vaccine is protective, but the shots will be tested in multiple places and multiple ways, “hoping that one of those will give us real data,” Dr. Bruce Aylward of the World Health Organization said.

Getting to that step is a story of nitty-gritty laboratory science, the kind that seldom makes headlines.

“You don’t know what’s going to be important 15 years from now,” noted Sullivan, a cell biologist who kept hitting roadblocks as she tried to unravel the mysteries of the immune system to create an Ebola vaccine. “You need a failure to know what immune responses aren’t helpful, as difficult as they were at the time.”

It started in the late 1990s, when Sullivan, who had just earned her PhD at Harvard, landed a job at the University of Michigan and began to develop an Ebola vaccine capable of protecting monkeys.

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Discovered in 1976, the virus cropped up every few years in remote parts of Africa. Early vaccine attempts had failed.

“The thinking was, this virus was too aggressive, it’s not possible to mount an immune response in sufficient time,” said Sullivan, who now heads biodefense vaccine research at NIH.

Most vaccines spur production of immune system antibodies that block a virus from entering cells, but Sullivan didn’t think that would be enough for Ebola, a large virus that infects in an unusual way.

Gene-based vaccines can induce additional virus fighters called T cells, so that’s what Sullivan created with pieces of Ebola genetic material. In July 1999, colleagues e-mailed that they’d given her vaccine to monkeys and measured a big immune reaction. In 2000, Sullivan reported in the journal Nature that four vaccinated monkeys survived an otherwise lethal dose of Ebola.

But her vaccine required multiple shots over several months, not useful during an outbreak. Sullivan scaled back, using a human cold virus, called an adenovirus, to carry the Ebola genetic material in one shot. Then she learned it wouldn’t work in people who’ve had that particular cold virus. Using rare human adenoviruses didn’t work at all; finally a chimpanzee cold virus did the trick.