They are three women who have spent months getting an experimental vaccine in the name of science. On each date of a strict timetable, they've headed to windowless exam rooms in Bethesda, Md., Baltimore and Atlanta and stuck out their arms, to get an injection or to have blood drawn. Or both.
How their bodies react will determine whether this clinical trial — one of the first — proceeds to the next stage in a long and complicated process. Its target is Zika, a virus that since 2015 has spread with a vengeance to 58 countries, infecting hundreds of thousands of pregnant women and putting their babies at risk of birth defects.
In Bethesda, volunteer Andrea Vaught is a researcher who is earning a master's degree in public health. Being part of a clinical trial appeals to her inner geek.
In Baltimore, volunteer Crystal Woodley is grateful for the $1,100 compensation, given her recent layoff from a night-shift warehouse job.
And in Atlanta, volunteer Virginia Bliss is motivated by love and gratitude for her 10-year-old daughter.
The trio is at the heart of an effort by scientists worldwide. At least six vaccine candidates are in the development pipeline in the United States, with drug companies and government institutions collaborating to accelerate the process.
There is special urgency with all this work. Zika has confounded the medical community with its unpredictability, and virtually every week, research provides disturbing new data about its damaging potential in the unborn, infants and even adults.
Yet vaccines usually take at least a decade to develop because so much of the effort is trial-and-error.
"When you are dealing with something that is going to require a response in a human body, which has so many variables … person to person," said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, "the chances for lack of precision and for something to go wrong is much greater."
Vaught, Woodley and Bliss are part of a trial led by NIAID. It may be the furthest along — having had no trouble attracting participants, particularly among women — and about 80 people have received multiple injections since August of the clear, colorless test preparation. By design, no participants are pregnant.
If things keep going smoothly, researchers hope to move to Phase 2 in February. That would involve trying the experimental vaccine in 2,400 to 5,000 volunteers in places where the virus is spreading to see whether it prevents infection.
• • •
On a cold, blustery morning, Vaught arrived at Building 10 — the Clinical Center — on the National Institutes of Health campus in Bethesda, for her second vaccine injection. From there, the 25-year-old would head to work at Georgetown University's Center for Global Health Science and Security, where she helps countries develop surveillance systems to prevent outbreaks.
"With everything going on in the world, I know I can sometimes feel powerless to do something," she said. "This is a small way to contribute to the development of a vaccine."
She hasn't had much of a reaction to the shots. After her first in September, she felt a little tired. But she wasn't sure whether to blame the vaccine or her schedule as a full-time research assistant and part-time student at George Washington University.
All participants receive the same dose — 4 milligrams of a small, circular piece of DNA, called a plasmid, in 1 milliliter of saline. It must be individually prepared each time.
New technology allowed NIAID researchers to engineer the plasmid so it contains genes coded for proteins of the Zika virus. When injected, a person's cells read the genes and make those Zika proteins, which in turn trick the body into mounting a defense with antibodies and T cells.
Such DNA vaccines don't have infectious material, so researchers say they can't cause a person to become infected with Zika; previous trials for other diseases have established their safety, but DNA vaccines haven't yet made it to market for human use.
• • •
Woodley was running late for her second shot in downtown Baltimore. Her ride didn't show. She didn't have time to wait for a bus. She took a taxi, arriving at the vaccine clinic at the University of Maryland School of Medicine at 10:50 a.m., almost an hour past her appointment time.
As soon as she walked in, Ginny Cummings, the no-nonsense study coordinator, picked up the telephone to notify the pharmacists to start preparing her dose.
Woodley took part several years ago in a malaria trial at the medical school, a study that required her to be in the hospital for nearly two weeks.
The experience piqued her interest, and she agreed to be contacted about future trials. The timing on this one worked well because she'd been laid off in April. She also welcomed the compensation, which depends on a volunteer's number of visits and the time needed to reach a facility.
"I really like what they're doing," Woodley said of the researchers, some of whom she knows from her previous trial. "It's to help people and prevent them from getting this disease."
Investigators say volunteers haven't reported any significant pain or unusual side effects. But interim data suggest their immune response "is lower than we would have expected," Fauci said. He describes it as "adequate, but not great."
Researchers have begun testing a variation of the DNA-based vaccine, which in monkeys generated a much stronger response than the original formulation. They began injecting it into a new group of 45 volunteers last month, again to watch for safety and immune reaction. "Already, it looks better," Fauci said.
• • •
Bliss, a longtime volunteer who started as a young mother a decade ago, is familiar with the routine of clinical trials and what's expected of her. The money earned has been helpful, she says, but participating also spurred an interest in science and biology.
"I really love being part of the process," said Bliss, 33, a histologist at Emory University's Yerkes National Primate Research Center, which conducts biomedical and behavioral studies.
Because Bliss does not plan to have more children, she says she would eagerly volunteer for another Zika trial — even if that meant becoming infected with live virus.
"I would absolutely sign up," she said. She knows it takes years to develop a safe and effective vaccine, but her hope is that by the time her daughter "is ready to have kids, Zika would have been eradicated. I believe there's a distinct possibility of doing that if we're all working together."
