In the fight against Zika, researchers are relying on lessons learned from battling dengue.
The fight against the Zika pandemic is full of moving targets. Among the more perplexing traits of this mosquito-borne virus are its obvious links to microcephaly in infants and the nervous disorder Guillain-Barré syndrome. Investigators are also noticing serious brain and spinal cord infections in people exposed to Zika.
As the demand for a vaccine intensifies, researchers are encouraged by a breakthrough in an older battle against a related foe: dengue. In a trial led by Bloomberg School researchers, the new dengue vaccine protected 100 percent of human volunteers. Associate professor and vaccine researcher Anna Durbin, MD, who led that study, discusses Zika’s unique challenges and the quest for solutions.
Months into the Zika outbreak, what remain as the biggest unknowns about the virus?
There are still some really big questions we need to answer. While Zika is fairly typical of flavivirus—a genus of viruses that includes West Nile virus and dengue—we haven’t seen a flavivirus that has effects quite like this. Zika’s affinity for the fetal brain is unique. West Nile can cause neurological illness like meningitis or encephalitis, but it’s generally in older people.
Recently the CDC has confirmed causality between Zika and microcephaly, however we still don’t know the extent. The possible link with Guillain-Barré syndrome is less clear. We need much cleaner data, which entails following people with and without Zika, to reveal the rates of Guillain-Barré. To me, all of this raises big questions about other flaviviruses: What characteristics do they have that we just don’t know about?
How do other mosquito-borne viruses like dengue help you understand Zika?
Through dengue, we are better able to understand and follow transmission. We know the seasonality of the mosquitoes and how long the virus lives in the blood. We can gauge the overall number of cases based on the number of symptomatic cases.
But the sexual transmission we’re seeing with Zika—we haven’t seen that with any other flavivirus. Now, that may be because we haven’t really looked for it; we haven’t had case reports of sexual transmission of dengue or West Nile. We don’t know how long Zika can be transmitted sexually, and if it’s a long time, that could be very problematic.
“I think it will be easier to make a Zika vaccine because it is only one virus, compared to dengue, which is four viruses. What’s going to be more difficult is deploying it.”
Your dengue vaccine trials are a major breakthrough. What might that vaccine mean for Zika?
For Zika trials, we are going to develop a human challenge model—which relies on healthy volunteers willingly exposed to the disease—similar to the one we used with dengue. That will help us choose which vaccines should move forward, and hopefully answer some of our big questions about the virus. We hope to have a Zika vaccine in human trials by the fall. We would test it in the U.S. first, looking at safety and the immune response. The most promising vaccine candidate will then likely be transferred to partners in Brazil for wider-spread testing.
I do think it will be easier to make a Zika vaccine because it is only one virus, compared to dengue, which is four viruses. What’s going to be more difficult is deploying it. A live vaccine would be cheaper to make than a killed vaccine, and it induces a broader response in the immune system. But we don’t know if a live vaccine will adversely affect a fetus the way the virus does. So we would have to ensure that pregnant women don’t get that vaccine; they would have to get a nonlive vaccine. So you’d have to make both and test women for pregnancy before giving the vaccine.
We see a future vaccine that combines Zika and dengue. Because if Zika dies down, like chikungunya has, there might not be a demand for a vaccine until there’s another outbreak. Combined with dengue vaccine, it’s commercially viable. It could be given to children as young as 1 year of age with the idea that by the time you reach puberty, you’re protected—much like how we administer the rubella vaccine. One of the advantages of live vaccines is that they do last a long time; how long can only be determined once the vaccine is in use.
How should we balance safety with the need for speed in vaccine development?
As we saw with the Ebola outbreak, by the time the efficacy trials were rolled out, the numbers of cases were so decreased that it was really difficult to establish efficacy.
It would be great if the World Health Organization, for instance, regularly made a list of what potentially are the primary emerging pathogens. If funding was available for early vaccine development, candidates would be ready. Then, when an outbreak is imminent, trial protocols can be rolled out quickly.
We’ve had a polio vaccine for six decades. Why are some viruses presumably easier to develop vaccines for than others?
Targeting a vaccine is largely pathogen-dependent, and relates to how well the pathogen is able to fool the immune system. The reason dengue has been so difficult is because you’re actually making four vaccines against four dengue viruses. If you don’t protect against all four, then you can actually make people worse. The problem with HIV is that the body makes antibodies to HIV, but those antibodies don’t work in the right way to prevent progression of the virus. So the virus has found a way to evade our own immune system. Some of it has to do with where the virus lives. Tuberculosis, for instance, can hide itself within the body, latently, and then emerge and cause disease.