Getting sick with the mosquito-borne Zika virus makes people more vulnerable to developing dengue disease later on, and to suffering from more severe symptoms when they do get sick from dengue, finds a new study published in the journal Science.

The study, which drew on data from two cohorts of Nicaraguan children who lived through a Zika epidemic in 2016 and a dengue epidemic in 2019, is the first to investigate the impacts of Zika immunity on dengue disease in humans.

Its findings confirm earlier suspicions that some antibodies to the Zika virus, which usually serve to protect the body from infection, may actually interact with dengue viruses in ways that can make dengue infection worse. This interaction, known as antibody-dependent enhancement, could make it harder for researchers to design a safe and effective vaccine that protects against Zika without also increasing the risk of dengue.

"The key thing that our study establishes is that prior Zika infection does significantly increase your risk of both symptomatic and more severe forms of dengue disease," said study first author. "That finding raises the questions: Could a vaccine only targeted at Zika actually put people at increased risk of more severe dengue disease? And how can you design a Zika vaccine that only induces good antibodies that protect you against Zika, but doesn't induce these other, potentially enhancing antibodies that are harmful against disease?"

The team drew on the pediatric cohort's bank of blood samples going back to 2004 to investigate other patterns of disease. It found that people who had one dengue infection, followed by a Zika infection, remained at high risk of developing a second, more severe dengue infection. In addition, when a person had two sequential dengue infections, the type of dengue virus that caused the second infection impacted whether the person was protected or experienced enhanced dengue disease.

"I think this can really help us understand epidemics that are coming down the line," the author said. "So, for instance, if you have a dengue Type 2 epidemic after a big Zika outbreak, you know to prepare your hospitals to treat people who might be more likely to develop a more severe disease."

When we get sick, our bodies produce large proteins called antibodies to help our immune system fight the infection. These antibodies have specific chemical shapes that allow them to stick to the pathogen of concern, flagging the invader to be broken down by immune cells. For viruses like Zika and dengue, they also can coat the virus and prevent it from entering the body's cells, effectively neutralizing it.

Antibody-dependent enhancement can happen when an antibody designed to stick to one virus, like Zika, tries to stick to a slightly different virus, like dengue. Antibodies to Zika virus can attach to dengue viruses, but not quite well enough to neutralize them. As a result, when a passing immune cell senses the antibody "flag" and tries to break down the dengue virus, it can actually end up getting infected by the virus.

"This mechanism not only allows the virus to get into more cells to infect, but also suppresses the immune response of those cells, enabling the virus to produce even more virus," another author said. "And, because they're immune cells, they are moving around the body. And so, they can initiate a larger infection."

Though this mechanism has complicated the search for effective vaccines for both Zika and dengue, the authors say that it is still possible to design vaccines that spur the body to create antibodies that only stick to the targeted virus, and no other.

https://news.berkeley.edu/2020/08/27/prior-zika-virus-infection-increases-risk-of-severe-dengue-disease/

https://science.sciencemag.org/content/369/6507/1123.abstract