In a small clinical trial led by the Johns Hopkins Bloomberg School of Public Health, researchers say that a promising single-dose dengue vaccine, developed by scientists at the National Institutes of Health, was 100 percent effective in preventing human volunteers from contracting the virus, the most prevalent mosquito-borne virus in the world. The findings, published March 16, 2016 in Science Translational Medicine, could be the final puzzle piece in developing a vaccine that is effective against dengue, which infects nearly 400 million people across more than 120 countries each year. While most of those who are infected with dengue survive with few or no symptoms, more than two million people annually develop what can be a dangerous dengue hemorrhagic fever, which kills more than 25,000 people each year.

Preventing dengue has been a particular challenge. A three-dose vaccine called Dengvaxia received limited licensure in 2016 in Mexico, the Philippines, and Brazil. That vaccine produced antibodies against the dengue in a clinical trial and protected against dengue during the first year after vaccination. But two years after vaccination, children who were under the age of nine when they received the vaccine were hospitalized for dengue at a significantly higher rate than those who received the placebo. For this reason, the researchers, led by Anna P. Durbin, MD, an associate professor in International Health at the Bloomberg School, were concerned that measuring antibodies alone may not truly indicate the ability of the vaccine to protect against dengue.

In February, based on the new findings, researchers in Brazil began administering the new single-dose vaccine in a large Phase 3 clinical trial designed to look at vaccine efficacy against naturally occurring dengue.

"Knowing what we know about this new vaccine, we are confident that it is going to work," Durbin says. "And we have to be confident: Dengue is unique and if you don't do it right, you can do more harm than good."

Dengue is marked by a high fever, with other symptoms including severe headaches, severe pain behind the eyes, rash and joint, muscle or bone pain. Dengue hemorrhagic fever occurs when blood leaks from the blood vessels into other parts of the body, which can lead to failure of the circulatory system and shock, and possibly death, without prompt, appropriate treatment. 

There are four very different strains of dengue that circulate and a successful vaccine must prevent all four strains. It has long been known that people who are infected once with one dengue virus are likely to get sicker if they are infected a second time with a different strain. For this reason, a good dengue vaccine needs to protect against all four dengue viruses, the researchers say.