One of the best ways to understand Zika virus might be to deliberately inject it into volunteers.
That idea may sound a little crazy, but it's not unprecedented. And some researchers are hoping the approach could help speed up the search for an effective Zika vaccine.
Right now, a bunch of labs are pursuing different ways of making a vaccine against Zika, mostly because of the concern that the virus might be linked to the birth defect called microcephaly.
At the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Maryland, scientists are creating different versions of a DNA-based vaccine. "Which one is the best one? We are testing it in animals, using that to select our top candidate," says Wing-Pui Kong, a virologist at the center.
If any vaccine candidate looks good in animal tests, it could then go for initial safety testing in people. After that, scientists somehow have to show that the immune response elicited by the vaccine will actually protect people from getting infected with Zika.
That's no easy task, and no one can say for sure how long it will take.
"Most vaccine development efforts are measured in decades," says Dr. Barney Graham, deputy director of the NIAID vaccine research center. "Almost every vaccine we have for a viral disease has come several decades after the discovery of the virus."
New technology does make it much easier to quickly develop a vaccine concept and test it in animals, he notes, "but you can't really have it for public use and distribution until you're able to prove efficacy. Proving that a vaccine works often takes very large organized field trials."
Those kinds of field trials are difficult, time-consuming, and sometimes just impossible. By the time an Ebola vaccine was ready to go into a large study, for example, the outbreak in West Africa was winding down. Not enough people were being exposed to Ebola to prove that a vaccine would protect them.
What's more, when researchers do manage to do a big clinical trial, it frequently reveals that their vaccine is a dud.
So, to see if a potential Zika vaccine really can protect people, scientists would like to do this: Give volunteers a candidate vaccine, and then later inject Zika virus into them, to see what happens. That could produce real answers fast.
"The limitations would be you'd have to do this in young people who were volunteering to do this and who were not going to get pregnant," says Graham.
In some ways, this is a blast from the past. In the 1950s, soon after Zika was discovered, one intrepid scientist injected it into his arm, to see if it could make people sick. He just got a slight fever.
After all, if you're not pregnant, "Zika itself is a pretty mild illness," says Dr. Anna Durbin, an expert on vaccine clinical trials at the Johns Hopkins Bloomberg School of Public Health.
This fall, we'll likely see safety tests of a potential Zika vaccine in about 20 to 50 people here in the United States. "And then the big question is, what is our next step?" says Durbin.
Ideally, she says, you could ask for volunteers to be exposed to Zika in a controlled setting. Researchers could compare two groups: people who get the virus alone compared to people who get a candidate vaccine and then the virus later on.
"We would admit them to our inpatient unit, where they have 24-hour care," says Durbin. And they'd use a low dose of the virus.
Her group has already done this kind of study to evaluate a potential vaccine for dengue, a closely related virus. Dengue can cause serious illness, but one particular dengue virus just causes a rash. And people did agree to be injected with it.
That let Durbin and her colleagues show that the dengue vaccine really seemed to protect people from infection, making them feel more confident about moving forward with larger trials.
"We would like to develop a similar model for Zika," Durbin says.
But the situation with Zika is a little more complicated. That's because, in addition to the possible connection with microcephaly in fetuses, Zika infection in adults may be linked to Guillain-Barre syndrome — a disorder in which the immune system attacks the nervous system.
"We do not want to put people at risk for that," says Durbin, "because these are normal, healthy people."
Still, people already face a small risk of getting Guillain-Barre from more mundane infections, like diarrheal diseases or the flu. And it's still unclear how often this actually happens with Zika.
That's something scientists are trying to understand now, to help them figure out whether it would be ethical to ask people to take a shot of Zika virus to help search for a vaccine.