Researchers are eager to test promising vaccines against Zika, the virus that sparked a global health emergency last year.
But uncertainty over whether the Zika epidemic will continue affects researchers' ability to finish testing vaccines. They need locations with an active viral outbreak to conduct large-scale human trials and make sure the vaccine actually protects against disease.
"On one hand, you don't want to see outbreaks of infection," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "But on the other hand, [without that testing] you might have to wait a long time to make sure that the vaccine works."
All the vaccines being tested are in Phase I clinical trials, which means they are being tested for safety in a small number of people. According to a review paper published Tuesday in the journal Immunity, the vaccines represent a variety of scientific techniques to thwart the disease, ranging from inactivating the virus to manipulating its DNA.
The NIAID announced Tuesday it is launching yet another Phase I trial for a vaccine made out of proteins found in mosquito saliva. The product is intended to trigger a human immune system response to the mosquito's saliva and any viruses mixed with it. If successful, the product could protect humans against a number of mosquito-transmitted diseases, including Zika virus, dengue and chikungunya. All three have infected people in the United States.
Col. Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research and co-author of the paper, says he expects preliminary reports on the safety of some of the older vaccines in April. As of now, he says, it is impossible to guess which vaccine will prove most effective in providing immunity.
"Sometimes it's difficult to predict which horse will win the race," Michael says.
Zika, which is spread from infected people to others by mosquito bites or sexual contact, often infects people without showing symptoms. In some cases it causes flu-like symptoms, such as fever, muscle aches and joint pain in adults ― and, in rare cases, Guillain-Barré syndrome, which can cause temporary paralysis. But it is most notorious for causing some children to be born with microcephaly, a devastating a birth defect in which a child's head and brain is smaller average size ― if their mothers were exposed to Zika.
The virus garnered international attention after hundreds of cases of disabled babies surfaced in Brazil. It quickly swept through South America and the Caribbean before stopping on the southern coast of the U.S.
Vaccines that meet the safety standard in Phase I clinical trials undergo subsequent rounds of testing to gauge effectiveness. To measure this, researchers rely on the gold standard of administering the vaccine to large number of people at risk to see if the vaccine is effective. However, Zika's recent arrival to the Western Hemisphere means researchers don't know whether the virus will become a perennial threat, or was a one-time explosion.
The uncertainty poses challenges for Zika vaccine development. A lull in the outbreak could cause significant delays in testing, pushing back the timetable for a commercially available product, Fauci says.
While researchers can use alternative methods to measure efficacy without large-scale testing, a decline in the circulation of the Zika virus could set progress back by years because the vaccine testing would be less reliable.
"If we don't get a lot of infections this season in South America and Puerto Rico, it may take years to make sure the vaccine works," Fauci says.
Fauci expects to launch the next round of human trials for a DNA vaccine developed by the NIAID next month.
Michael also worries that a lag in the number of Zika cases could lead the private sector to pull funds from vaccine development. It takes millions of dollars to develop a drug or vaccine, and pharmaceutical companies play a critical role in making and manufacturing them, he said. But those companies have many competing interests, he notes, and if it is hard to test a vaccine this year, federal agencies and private companies may turn their Zika prevention efforts elsewhere.
"This is a constant issue, where you put your resources," Michael says.
So far, signs suggest that the climate could be ripe for Zika again this year. Warmer-than-usual temperatures are affecting areas across the Western Hemisphere, including hotbeds of the Zika outbreak in Brazil. The National Oceanic and Atmospheric Administration found that South America experienced the second hottest January in recorded history.
The balmy temperatures rev up the Aedes aegypti's behavior in multiple ways, says Grayson Brown, professor of entomology at the University of Kentucky. They tend to move faster, lay more eggs per day and feed more frequently. However, the heat is not necessarily correlated to higher numbers of the mosquito, Brown says, as they tend to live among humans, not in the wild.
"This mosquito breeds almost exclusively in human created containers," he says. "You don't really find it out in the woods."
In the United States, areas with populations of the Aedes aegypti are closely monitoring their numbers. Last year, Texas and Florida dealt with locally acquired cases of Zika infection.
In Texas, public health officials have monitored mosquito populations throughout the winter to track their numbers and any presence of the virus. Despite unseasonably warm weather, Chris Van Deusen, spokesman for the Texas Department of State Health Services, says they have seen lower numbers of the Aedes aegypti and no cases of Zika.
Van Deusen says the state is also monitoring the outbreak in Mexico, since heavy traffic across the border increases the possibility of transmission in Texas. Officials are expecting another outbreak of locally transmitted cases of disease, Van Deusen says.
But when and where? That's a mystery. "There's so many factors that go into it, it's really impossible to make an ironclad prediction," he says.