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Scientists injected people with the dengue virus to test a vaccine

And they want to replicate the research to study Zika

Amelia Krales

Every year, mosquito bites cause up to 400 million dengue virus infections — but an experimental vaccine developed by the NIH could change that. Though the study of the vaccine was small, its results were promising.

A single dose of the vaccine protected all 21 people in a small trial from dengue, according to results published today in Science Translational Medicine. In contrast, the 20 people who received a placebo all developed signs of dengue after being intentionally exposed to a modified version of the virus. Because of the trial's success, scientists think a similar approach could help researchers develop a vaccine for the Zika virus.

A single dose protected participants from a deliberate injection of dengue

About half the world’s population lives in areas with dengue. As a result, an estimated 500,000 adults and children are hospitalized every year by the most severe form of the disease, and about 12,500 people die. There are four different types of dengue, and no cure exists for any of them. That's why researchers have been working on developing a vaccine.

So far, only one dengue vaccine has been approved, and its use is limited to people over the age of nine in Mexico, the Philippines, and Brazil. That’s because even though it works on adults, studies have shown that the vaccine actually increased the likelihood of a child under the age of nine being hospitalized for dengue two years later. In light of these findings, researchers at the NIH decided to test another candidate vaccine in a controlled setting, on a small number of people.

This trial involved deliberately injecting people with a form of dengue, a style known as the "challenge study." In this case, scientists used a modified form of a dengue type 2 virus that only produces minor symptoms, like rashes. The people who were in the placebo group all developed signs of the illness following the exposure. But people who got the vaccine six months before the dengue challenge developed no symptoms at all — no rashes, no drop in their white blood cell count, and no signs of the virus in their blood.

It’s not clear how the vaccine will work in the real world

This is a very promising result, but it’s not clear what that will mean in the real world. Testing a vaccine against a modified virus like the one used in this trial is very different from testing it against a fully functional virus, says Annelies Smith-Wilder, an epidemiologist at Nanyang Technological University in Singapore who didn’t work on the trial. So even though researchers think the dengue vaccine works, they don’t know for sure — at least not yet. "The only way to validate this is to actually see how the vaccine will perform in the field and if the findings with the human challenge study are valid or not," says Timothy Endy, chief of the infectious disease division at SUNY Upstate Medical University.

The NIH's researchers know this and they’re already working on a larger trial for the vaccine. Last month, they started one in Brazil where dengue is common; scientists hope to enroll 17,000 adults, adolescents, and children, Durbin says. A second challenge study, this time for dengue type 3, is also underway.

"There is an urgent need for a Zika vaccine."

But even without results from those trials, the researchers say the challenge study's success could extend beyond dengue; a similar study could be applied to the Zika virus. "There is an urgent need for a Zika vaccine," Anna Durbin, an infectious disease expert at Johns Hopkins Bloomberg School of Public Health who worked on the trial, told reporters during a press conference yesterday. "We are looking at strategies to really accelerate that timeline, and we think that a Zika human challenge model could be very useful in that endeavor."

Purposefully injecting people with a mild form of the Zika virus to better understand the illness is an interesting idea. Even though the virus was discovered in 1947, scientists know distressingly little about it. So a challenge study could not only help researchers develop a vaccine, but also learn about the disease itself, Durbin says. But the same issues would likely arise; until a drug is tested in an area where people are likely to become infected with Zika, scientists won’t know if they’re working on something that’s medically useful.

Pharmaceutical companies are already interested in the dengue vaccine

Though people do have doubts about the challenge study method, development on today’s dengue vaccine is moving forward. In India, two companies are pursuing its development, whereas in Brazil, the Butantan Institute has obtained the exclusive rights to the vaccine, Stephen Whitehead, senior associate scientist in the laboratory of infectious diseases at NIH, told reporters. Merck & Co. holds exclusive rights in the US and Canada, he added. "The US government has made the vaccine materials and technology available for licensure across the world — and we've had several licensees come forward."