The prestige of solving the puzzle and the chance to save lives are possible rewards. For the companies, another motive is the potential for significant profit. Unlike many recent viral outbreaks, which have been confined to poor areas, Zika has spread to countries like Brazil and the United States, with millions of wealthy people and governments that can afford public vaccination campaigns.
“It’s highly unusual,” said Dr. Thomas P. Monath, the chief scientific officer and chief operating officer of NewLink Genetics, one of the companies developing a vaccine. “It reflects the big opportunity and public health need, and also the fact that we have more, different technologies available today.”
But meeting the ambitious timeline is far from guaranteed. To keep the fast pace, some clinical trial organizers are trying to start their tests in South America over the next few months, when Zika infection rates are expected to be at their height there.
The timing is crucial. An outbreak of Zika provides an ideal testing ground for a vaccine, so the preventive medication can be evaluated in a population exposed to the virus. Researchers will know in short order whether the vaccines being tested are effective.
If they miss the window, a vaccine could be delayed for a year or more — a result that could lead to millions more people becoming infected with the virus.
“It’s a race against nature,” said Michel De Wilde, a vaccine research consultant and former executive at Sanofi, a French vaccine manufacturer.
The virus, spread by mosquitoes and sexual intercourse, has now been reported in more than 70 countries. This summer, it landed in the United States, spreading quickly in Puerto Rico and turning up in Miami. Government officials have advised pregnant women to avoid parts of Miami where the virus is active. In a sign that Zika will be a continuing threat, on Friday the World Health Organization lifted its nine-month emergency declaration and said it would shift to a longer-term effort to combat the virus.
By September, after acrimonious debate and a long delay in Congress, President Obama approved a $1.1 billion spending package to fight the virus. About $400 million of the money will go toward developing a vaccine and diagnostic tests.
The escalation of attention has been remarkable. Identified nearly seven decades ago, Zika was once considered mostly harmless, because about 80 percent of people who are infected show no symptoms.
But about 18 months ago, Brazilian officials began to sound alarms that it was to blame for an otherwise mysterious outbreak of babies born with microcephaly, or unusually small heads and malformed brains. Around the same time, heartbreaking photographs of children born with the condition shot around the globe.
Dr. Barney S. Graham, deputy director of the Vaccine Research Center at the N.I.H, was at a meeting in July 2015 when he learned of the threat. A Brazilian doctor pulled him aside at the meeting in Bethesda, Md., which had been called to discuss chikungunya, another tropical disease.
“I know we’re here about chikungunya,” Dr. Graham said the doctor told him. “But I really want to tell you about Zika virus.”
Within months, the link seemed increasingly clear, and public health officials predicted that the virus would probably infect millions of people. In December, Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases at the N.I.H., called a meeting with the top members of his vaccine staff.
Similar meetings were occurring elsewhere in the vaccine world — at small companies like Inovio Pharmaceuticals and NewLink, in the offices of big manufacturers like GlaxoSmithKline and Sanofi, and at the Walter Reed Army Institute of Research, which is a few miles from the N.I.H. campus in Bethesda, where Dr. Fauci’s team works.
“I said, all hands on deck,” Dr. Fauci recalled. “We have a serious problem here. We’ve got to really move.”
High Stakes and Confidence
No single person directs an operation as widespread as the race for the Zika vaccine. But Dr. Fauci certainly sits near the center of it and comes with a singular perspective.
An immunologist, Dr. Fauci, 75, has led the National Institute of Allergy and Infectious Diseases for more than three decades, playing a role in nearly every major disease outbreak since the 1980s.
And to hear him tell it, the Zika virus does not stand much of a chance.
“Without being presumptuous, most of us in the field feel that we will get a vaccine for Zika,” Dr. Fauci said recently, his staccato Brooklyn accent underscoring his confidence. “So it’s really a question of what’s the best one, how quickly can you get it, is it safe, and is it scalable?”
But he also knows the stakes.
“For a pregnant woman,” he said, “it’s absolutely devastating in its potential impact.”
His team, and the others chasing a Zika vaccine, started with a couple of big advantages. For one, the economic incentives are clear. The first company to develop an effective vaccine will win a toehold in a market that could ultimately reap billions in profit. And because governments are paying for some of the early development, the financial risk is limited.
Also, the disease belongs to a family of viruses known as flaviviruses, which scientists have been battling for more than a century. Vaccines already exist for some of these viruses, such as yellow fever, Japanese encephalitis and dengue.
Another good sign: Adults infected with Zika seem to fight off the illness on their own, meaning the human body, if given the right tools, already has the resources to defeat it.
The vaccine hunters had several options. The tried-and-true method is what is known as a killed vaccine, in which a dead virus is injected into the body. The body then builds its defense against the virus in a way that also protects against the live version. This is how many vaccines work, including those for polio and the flu.
Several teams, including those at Takeda and one at Walter Reed, chose that path. Walter Reed’s candidate entered early clinical trials in this month. Sanofi has signed on to bring that product to market.
The advantage of the killed vaccines is that they are reliable. Several vaccine specialists said they were confident a Zika vaccine using this method would succeed. The downside is that developing one takes time, sometimes decades.
Other teams, including Dr. Fauci’s scientists at the N.I.H., decided on a newer approach. It involves manufacturing a harmless piece of the virus’s DNA, the molecule that acts like an instruction manual for the body. Once injected, the DNA tells human cells to make Zika proteins. Those proteins then assemble themselves into harmless viruslike particles that trick the body into developing antibodies that can fight the disease if it arrives.
It is a startlingly simple and fast approach. Dr. Fauci’s team created a prototype that it could begin testing in mice within weeks.
“You can jump in right away,” he said.
However, DNA vaccines are largely unproved in humans. While the technology has been approved for animals, none of the vaccines have been approved for humans. A vaccine developed by the N.I.H. to prevent West Nile, another virus related to Zika, succeeded in early trials but never completed trials and was not brought to market because researchers could not find a drug company that was interested.
Part of the reason DNA vaccines are tricky, researchers say, is because the vaccine’s DNA must reach the nucleus of a person’s cells before it can begin instructing them to make Zika proteins. When the vaccine is injected into the body, not all of it reaches the nucleus, lowering its effectiveness.
To solve this problem, some companies are trying a similar method that uses RNA, a molecule in the body that is more flexible than DNA. Among the things it can do is carry out, on its own, the instructions contained in DNA. The vaccine would not need to reach a cell’s nucleus to trigger the immune response.
GlaxoSmithKline and Moderna Therapeutics, using government grants, are working on RNA vaccines for Zika that are still in their early stages.
Testing in Zika Zones
If one or more Zika vaccines are successful, it is unclear who would ultimately get them. The medication could be used only during outbreaks, or it could become routine in some parts of the world.
Early trials of the DNA-based vaccine developed by the N.I.H. are underway, and studies have begun in Puerto Rico of a similar vaccine being developed by Inovio.
The next step will be to test the vaccines in a larger pool of people who live where Zika is present. That stage must be intricately set so that the trials occur at just the right moment, at the height of summer in Latin America, which starts in December.
Not a day can be wasted. The N.I.H.’s trial coordinators are setting up trial sites at more than 20 locations in Central and South America. Once the trials begin, the coordinators will monitor local Zika cases, moving resources to sites of outbreaks and away from places where the virus is quiet.
Researchers say they are taking a lesson from the Ebola outbreak of 2014, which also spurred a race for a vaccine. In that case, the outbreak was brought under control before many of the trials could take place.
“All of us felt like we kind of really missed the boat with Ebola,” said Col. Nelson Michael, who is leading the Zika vaccine effort at Walter Reed. “We brought troops too slowly into the fight.”
In a clinic at the University of Maryland in Baltimore in September, several volunteers waited hours in a hallway to be among the first to receive the experimental DNA vaccine being developed by the N.I.H.
Some read college textbooks, others browsed Facebook.
Jen Wenzel, a volunteer and a postdoctoral fellow in neuroscience, said she signed up out of curiosity — and to make extra money. Volunteers are paid as much as $1,600 if they complete the study.
When it was her turn, Ms. Wenzel winced and looked away from the needle about to deliver the vaccine. “Take a deep breath,” said a nurse, who then quickly jabbed the needle into Ms. Wenzel’s arm, making her gasp in surprise.
And with that, Ms. Wenzel became the 29th person at the University of Maryland, and one of only dozens worldwide, to have received a potential Zika vaccine. Over the next two years, she will return to the clinic for follow-up tests to see how well it works.
Of course the researchers chasing a vaccine — and the many millions of people concerned about catching the virus — hope to have an answer long before then.