Valerie Pavilonis

A joint Yale study with the Brazilian Ministry of Health found a link between dengue infection and Zika protection.

In 2015, a group of Yale researchers were studying urban slum health problems in northeastern Brazil. But when the Zika virus spread throughout the region, they were in the perfect place to investigate how it works and who was infected. Using blood samples and questionnaires from their work before the outbreak, they found that Brazilians who had already been infected by dengue had a significantly lower chance of contracting the Zika virus. This finding is a crucial step in developing a Zika vaccine, according to the researchers. The study was published in the journal Science on Feb. 8.

“We had the unfortunate or unique opportunity to really study the outbreak as it happened because we had already been doing prospective studies,” said chair of epidemiology at the School of Public Health and senior author of the study Albert Ko.

According to Ko, the epicenter of the Zika epidemic was Salvador, Brazil, where his team performed their tests. Several months after the outbreak, he said, pregnant mothers gave birth to babies with microcephaly, a condition where babies’ heads are abnormally small due to stunted brain development.

After making the connection between Zika and microcephaly, his team started analyzing the data they had collected before the outbreak to find biological clues for a potential Zika cure. One link they found involved dengue.

Dengue and Zika are part of the same virus family — called flavivirus — which also includes West Nile virus and yellow fever. Carried primarily by mosquitos, dengue also has an ability to enhance itself when antibodies are present. This means that the first time someone gets dengue, the body develops antibodies to fight it, but the second time, these antibodies will make symptoms even worse.

“One of the questions that we wanted to ask was that since Zika and dengue are kind of similar,” Ko said, “if you had a previous infection with dengue, do you end up getting sicker or having a higher risk of getting infected when you got Zika?”

Curiously, according to the study, dengue antibodies did not have the same effect on Zika. Rather, they protected the body from getting infected.

“What we found was that the higher the level of antibodies you had against dengue, the lower the risk you had of getting an infection,” he said.

However, according to Ko, this finding comes too late to impact the Zika epidemic of 2015. In Salvador, 73 percent of the population was infected with the virus. Since such a large proportion was infected, he said, the virus ran out of new hosts and eventually died out. Now that most of the residents are now immune, those in Salvador who are most at risk for getting the disease — childbearing-age women — don’t have to worry. This is what biologists call herd immunity.

Ko said that even though herd immunity is present in Salvador, there may be a risk of another epidemic in other places in Brazil, and thus more chances to test Zika vaccines.

“The epidemic came like wildfire, but we still may have pockets that may sustain transmission in the future, where everyone wasn’t infected and there’s not a high level of herd immunity,” he said.

Because of antibody-dependent enhancement, developing a vaccine for dengue — and, by extension, Zika — is more complicated than injecting weakened forms of the virus into the body, like doctors do for chickenpox or measles. As such, School of Public Health epidemiology professor and co-author of the study Frederico Costa said his team has more work to do to explore how to harness these results in a way that can contribute to making a safe vaccine for both viruses.

“Those findings could have implications for approved and experimental dengue vaccines,” Costa said. “However, other studies focusing in vaccine efficacy against those two viruses are needed.”

According to the Centers for Disease Control and Prevention, Zika was discovered in 1947.

Matt Kristoffersen | matthew.kristoffersen@yale.edu

Correction, Feb. 12: A previous version of the article stated Albert Ko was the chair of epidemiology at the School of Medicine. In fact, Ko is the chair of epidemiology for the School of Public Health.