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n experimental dengue vaccine protected 100 percent of people when it was put to the test in a clinical trial, researchers reported Wednesday, a significant finding in the quest to battle a disease that infects an estimated 400 million people a year.

Vaccinated and unvaccinated volunteers were injected with mild dengue viruses in an attempt to see if the component of the vaccine meant to protect against a particular strain actually works. In the trial, all unvaccinated trial participants became infected; none of the vaccinated volunteers did.

The study findings are promising for the US-designed vaccine, which is already being tested in a larger, more advanced trial in Brazil.

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They are also encouraging for scientists seeking to accelerate development of a vaccine for Zika virus. The trial was a so-called “human challenge study,” which allows scientists to assess the effectiveness of a vaccine much more quickly than traditional studies but which is only permitted in the case of illnesses that are mild or treatable.

The research team behind the dengue study said it wants to develop a human challenge model to study what the Zika virus does when it infects people, and use the approach to fast-track vaccine development. Both diseases are spread by Aedes mosquitoes.

Leading dengue expert Dr. Scott Halstead applauded the use of this approach for this vaccine.

“I think it’s widely considered to be safe. It’s considered by me to be smart,” said Halstead, a longtime US Army scientist who is now retired but continues to work in the field.

The results of the dengue study were published in the journal Science Translational Medicine.

The research team — involving scientists from the National Institute of Allergy and Infectious Diseases, the vaccine initiative at the Johns Hopkins Bloomberg School of Public Health in Baltimore and the University of Vermont — is now conducting a challenge study using a component of the vaccine known as dengue 3.

Halstead said it made sense that the group started with dengue 2. There had been fears it might be a weak link in the vaccine, he said.

There are four strains of the virus; infection with one dengue virus does not protect against the other three. In fact, it can increase the risk of the infected person will develop the more severe dengue hemorrhagic fever. It is estimated about 25,000 people die of this condition every year.

That phenonomen — prior infection enhancing rather than reducing the risk of severe disease — complicated efforts to devise an effective and safe dengue vaccine. Work on the vaccine in this study started more than 15 years ago.

One dengue vaccine — made by Sanofi — has made it to market in several Latin American countries and the Philippines. But despite the fact it triggers good antibody production, the protection the Sanofi vaccine offers is modest. And young children who received it in clinical trials were more likely to be hospitalized for serious dengue illness two years after vaccination than children who received placebo shots.

A huge problem with the development of a dengue vaccine is that scientists still don’t know what parts of an immune response must be activated for a person to be protected. They haven’t yet figured out what are called the “correlates of protection.”

“They are not known. We have none,” said Halstead, who was not involved in this research.

So the researchers decided to turn to the challenge approach, enrolling 41 volunteers at the University of Vermont’s vaccine testing center in Burlington. This technique allowed them to see what happened when people were exposed in nature to a disease-causing agent.

“This information would be otherwise much longer in coming, it would have to be done and found out through a lengthy field trial, in a disease endemic area, which would take three to 10 years and probably tens of millions of dollars,” said Dr. Beth Kirkpatrick, director of the vaccine testing center.

The vaccine was designed at the Laboratory of Infectious Diseases at the National Institutes of Health. It’s a live attenuated vaccine, meaning it contains actual infectious viruses that have been weakened.

The goal is for the vaccine viruses to be strong enough to infect — which is necessary to prompt the immune system to see the threat and develop defenses against it — but mild enough that the viruses don’t actually make recipients sick.

The success of this study is inspiring the team to think about what could be learned about the Zika virus using a human challenge approach. Dr. Anna Durbin, the senior author of the paper, said they think it can be done.

“We believe that a safe Zika human challenge model can be developed and would be instrumental in the acceleration of Zika vaccine development,” said Durbin, an associate professor at the Johns Hopkins Bloomberg School of Public Health.

“I think the other real potential for a Zika human challenge model is to better understand Zika itself.”

A few aspects about where you live can help determine that. Alex Hogan/STAT

 

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