At any one time, scientists in the Vanderbilt Vaccine Center are working on projects relating to 50 different target viruses. When an outbreak of a virus hits, the vaccine center researchers ramp up their efforts, as in the case of Ebola last year and Zika virus over the last few months. Zika has received increased attention recently since the World Health Organization declared a Public Health Emergency of International Concern in response to an outbreak in the Americas.
According to James Crowe, Director of the Vanderbilt Vaccine Center, the lab has been researching the Zika virus for about a year now in hopes of creating an antibody treatment.
“[Zika virus] wasn’t highest on our list because it just wasn’t very common,” Crowe said. “We have ongoing large projects that are particularly current and then a lot of little [projects] percolating. This is one we were already starting to work on, and that’s how we got on to such a good start.”
Background on Zika
According to Crowe, Zika virus was first discovered in Africa in 1947. The mosquito-borne virus is spread by a type of mosquito called Aedes aegypti. Four out of five people infected with Zika virus experience no symptoms at all, Crowe said. The 20 percent who do experience symptoms report fever, rash, joint pain, swelling, red eyes (conjunctivitis) and flu-like symptoms.
“That usually only lasts for a few days, so it’s usually a mild illness, and very few people die of it,” Crowe said.
Zika’s more serious symptoms are found in pregnant women. In the areas where Zika virus has been present, especially in Brazil, doctors noticed an increase in microcephaly, a condition where babies are born with small heads, in addition to more cases of Guillan-Barre, a brain condition that affects unborn babies.
“It’s not fully proven, but it’s suspected that infection with the virus is occasionally associated with these two things, and these are the severe things people are worried about,” Crowe said.
As far as we know, according to Crowe, if one does not have microcephaly or Guillan-Barre, it is not clear that there are any long-term effects from the Zika virus.
“But those two conditions can be debilitating, and, of course, microcephaly, those kids may never walk or talk,” Crowe said. “They really have very big challenges.”
Evidence shows that the virus lasts about a week before one’s body clears it. If a person is previously infected with Zika virus and later becomes pregnant, no harm will be done to the baby, as far as scientists can tell right now.
Zika Research at Vanderbilt
Crowe’s laboratory can take the blood of people who are infected with Zika virus and pull out virus-specific antibody cells. Crowe’s lab already had immune donor cells prior to the recent outbreak, which put them in a good position to accelerate their Zika research.
“Once we have those individual cells, we can use the genes from those cells to make that antibody protein,” Crowe said. “It turns into a drug basically and we can make unlimited amounts of it. So they are naturally occurring drugs based on your normal immune system, but we get them from immune donors.”
These antibodies can be administered to another person and provide a temporary prevention strategy.
“So if you were a traveler and you went, say, to the Olympics, you would take this sort of drug and it would cover you for the several weeks that you were there,” Crowe said. “If you are living in an [affected] area, you would need to take the drug again about every three or four weeks.”
These antibodies can also be used for treatment, particularly for pregnant women or women of childbearing age who are infected. Crowe’s lab is collaborating closely with the lab of Michael Diamond at Washington University in St. Louis.
“He is a world expert on mosquito-borne viruses and animal models, so he is working on mouse models of Zika virus infection in pregnancy,” Crowe said.
Crowe anticipates having drug candidates within about two months, at which point a lot of work will need to be done to show that the drugs are safe and effective. In the best case scenario, Crowe says the lab’s treatment could enter clinical trials in about a year’s time.
There are two routes these drugs might take in becoming available to the public. One of these routes is compassionate use, in which the drug is offered to people while warning them that it has not yet been proven safe or effective, but it is reasonable to think it might be.
“Generally we want to do trials to see if [the treatment] actually is safe and works, but [during outbreaks], there is very intense pressure on those who have these sort of drugs to make them available for compassionate use,” Crowe said.
The other route is that of four-phase clinical trials to show that the drug is safe and effective.
“That could happen very rapidly if you have a very brisk outbreak and you go in and treat everyone in the city with an antibody or a placebo, and you see a major effect in hundreds or thousands of people, then you’re done,” Crowe said. “But often this can take years. It just depends on how well the team executes.”
According to Crowe, the traditional clinical trial route is preferred because it allows for data gathering. In compassionate use settings, not enough numbers are gathered to determine whether the treatment was effective, so little progress is made.
Traveling to affected areas
The principle concern regarding Zika virus, according to Crowe, is for those who are pregnant or could become pregnant and are going to exposed areas.
“So either the strategy would be to avoid pregnancy, or the CDC has recommended that women who are pregnant not travel to these areas,” Crowe said.
The other action one can take to reduce risk is to avoid mosquito bites by wearing proper clothing and good insecticides, particularly those that contain DEET.
In regard to traveling to affected areas, Crowe noted that over a million people travel from the U.S. to the Caribbean every year, and that traveling to these areas is a personal choice.
“Given that for most people, even if they are infected, it is asymptomatic, and those who do get infected, it’s a brief mild acute illness, I think you just have to just consider that risk for yourself,” Crowe said.
According to Crowe, Zika virus is not the only virus exposure people should be thinking about. Chikungunya, which has been another subject of research in Crowe’s lab, has caused large outbreaks in some of the same areas in the last year. Another mosquito-borne illness, called dengue, is also prevalent in these areas.
“So rather than just worrying about Zika, you want to avoid mosquitos because of all these other things,” Crowe said. “The other viruses are still going on, and they are important, they are just not in the news right now. It does raise consciousness about avoiding mosquito bites in these areas.”