Inovio Pharmaceuticals's DNA vaccine uses plasmids (green circles) to carry Zika genes into cells, which produce viral proteins. IMAGE: INOVIO PHARMACEUTICALS

When it comes to making vaccines, not all viruses are created equal: Some, like HIV, notoriously find ways to outmuscle the immune responses raised by a vaccine. This week, new studies in monkeys put Zika virus squarely in the wimp corner, welcome news as the first human vaccine trial against it begins.

A vaccine is sorely needed. The virus has blasted through Latin America, leaving severe birth defects and other maladies in its wake. Just this week, Florida health officials confirmed the first cases of local transmission in the United States; until now, all cases here involved people who had traveled to affected countries. These Florida cases were mainly infected by mosquitoes within a 2.5-square-kilometer area of northern Miami.

Since Brazilian health officials first reported local transmission of Zika virus in May 2015, researchers have been scrambling to develop a vaccine. The monkey studies, published online this week in Science, suggest that outwitting Zika virus should present few obstacles. A research team from the Beth Israel Deaconess Medical Center in Boston and the Walter Reed Army Institute of Research in Silver Spring, Maryland, vaccinated 16 monkeys with three experimental vaccines and then “challenged” them with injections of Zika virus. As a control, they challenged 12 unvaccinated monkeys. None of the vaccinated monkeys became infected, whereas the Zika virus rose to high levels in the blood of all of the control animals. “The protection was striking, and it certainly raises optimism about development of a Zika virus vaccine for humans,” says Dan Barouch, an immunologist at Beth Israel who co-led the studies.

The group tested three different approaches. One is a traditional vaccine that uses a whole, killed Zika virus. The second contains DNA from Zika woven into a small, harmless circle of DNA called a plasmid; once in cells, this DNA produces Zika proteins that spark an immune response against them. The third strategy stitched Zika genes into adenoviruses, which act as Trojan horses and infect cells to trigger immune responses.

Barouch stresses that his group's data do not predict which vaccine will work best in humans. “The goal of the study was not to have a cook-off of different vaccine modalities,” he says. Instead, a key aim was to identify which components of the immune response correlated with protection against the virus to help guide human trials. Specifically, the monkey studies showed that even low levels of antibodies directed toward the Zika virus completely protected the animals.

On 26 July, Inovio Pharmaceuticals, a small company based in Plymouth Meeting, Pennsylvania, began the first human trials of a Zika vaccine. The biotech's DNA vaccine is being tested in a phase I study on 40 healthy people for safety and its ability to trigger immune responses. Others are in the works. The National Institute of Allergy and Infectious Diseases (NIAID) in Rockville, Maryland, is collaborating with the Walter Reed group, the Butantan Institute in São Paulo, Brazil, and the pharmaceutical company Sanofi Pasteur in Swiftwater, Pennsylvania, to develop three other Zika vaccines, including one that also uses Zika DNA alone and will likely enter human studies within the next few weeks.

NIAID Director Anthony Fauci says the monkey results are “encouraging” and add to other evidence that “strongly suggest we'll get an effective vaccine.” But determining whether any Zika vaccine works in humans may present tricky challenges. Researchers hope to fast track vaccines that pass muster in phase I studies and go straight into efficacy trials in a few thousand people in regions of Latin America where the virus has spread rapidly. If all goes well, those prevention trials could start as early as the beginning of 2017 and determine within a year whether the vaccines protect people.

But Neil Ferguson, a mathematical modeler at Imperial College London, thinks the epidemic is racing so fast through Latin America that many people may have been exposed and become immune by the time efficacy trials begin, leading to a drop in transmission rates that, in turn, make it far more difficult to see the benefit of a vaccine. A similar drop hampered some vaccine trials during the Ebola epidemic in West Africa. Ferguson, who led a team that recently modeled the spread of Zika in Latin America (Science, 22 July, p. 353), says the virus has already peaked in Brazil and Colombia and that infected people will likely develop lifelong immunity. “My gut instinct is the way the epidemic is moving, by the end of next year there'll be very little Zika left there.”

Ferguson suggests that instead of setting up vaccine trials in one place, researchers could run sequential trials in different populations. “We need to be ready to restart trials when new outbreaks are seen,” he says.

Fauci, however, expects to see large numbers of new Zika infections in South America for several years. It's now winter in much of the continent, which explains why cases have precipitously dropped, he says, and he doubts that the level of so-called “herd immunity” in the population will significantly lower the spread of the virus there next summer when mosquito populations swell. “The second wave I'd assume is going to be less robust, but there's still going to be enough infections to get an answer from vaccine trials,” Fauci says. “Unlike Ebola, Zika is not going to disappear.”